Learning Center: ORAL MUCOSAL LESIONS

Last reviewed: October 3, 2026

Summary

The mouth is lined by a thin, moist tissue called the oral mucosa. A sore, white or red patch, blister, ulcer, or burning area in that lining is an oral mucosal lesion. Most are harmless and short-lived, such as a bite injury or a canker sore. Others are a sign of a condition elsewhere in the body, an infection, a reaction to something that touches the mouth, a side effect of medicine or cancer treatment, or, less often, a precancer or cancer.

Oral mucositis is a specific kind of mouth soreness caused by radiation or chemotherapy. It affects about 80% to 90% of people treated with radiation for head and neck cancer, and about a third to two thirds have severe mucositis [1, 2]. It is temporary, but it can make eating painful and can interrupt cancer treatment.

Any sore, ulcer, or white or red patch that has no clear cause and does not heal within about two weeks should be examined, and many need a biopsy. Brushes, dyes and lights cannot replace a biopsy [3, 4]. The sections below explain the main causes of oral lesions, how they are evaluated, and what helps, including the studies behind each point. A numbered reference list is at the end of the page. Where the evidence is limited or mixed, the page says so.

Introduction: the lining of the mouth

The oral mucosa covers the inside of the cheeks and lips, the tongue, the floor of the mouth, the gums and the palate. Its surface is a layer of flat cells (squamous epithelium) that is constantly renewed from below, which is why the mouth usually heals quickly. That same constant cell division is why the lining is so easily injured by radiation and chemotherapy [5]. Saliva keeps the lining moist, washes away food and microbes, and buffers acid. When saliva is reduced, the lining becomes fragile and prone to soreness and infection [6].

The lining on the gums and hard palate is thick and tough (keratinized). The lining of the cheeks, the sides and underside of the tongue, the floor of the mouth and the soft palate is thin and more easily injured. These thin areas are more easily injured by radiation [7], and leukoplakia on the side of the tongue carries a higher cancer risk than leukoplakia elsewhere [8].

A few terms are used throughout this page. An ulcer is a break through the surface layer. An erosion is a shallower loss of surface. Leukoplakia is a white patch that cannot be wiped off and has no other identifiable cause. Erythroplakia is the red counterpart. A biopsy removes a small piece of tissue for examination under a microscope. Direct immunofluorescence is a special stain on a biopsy that shows whether the immune system is attacking the lining, which is how blistering diseases are diagnosed [9].

The PowerPoint below explains how mucositis from cancer treatment is diagnosed, graded and treated. Its author, Patrick J. Stiff, MD, was also an investigator in the palifermin trial described later on this page [10].

PowerPoint on the diagnosis, severity grading, treatment, and coding of oral mucositis by Patrick J. Stiff, MD.

Differential diagnosis of oral mucosal lesions

The causes of oral mucosal lesions fall into the groups below. More than one cause is often present at the same time. For example, a person with a dry mouth from medicines may also develop thrush, and a person with lichen planus may also be irritated by toothpaste. The three most common oral conditions seen in general practice are dry mouth, oral candidiasis (thrush) and recurrent aphthous ulcers (canker sores) [6].

1. Metabolic, systemic and endocrine causes

The mouth often shows signs of a disease elsewhere in the body. Sometimes the mouth is the first place it appears, and the oral findings can track how active the disease is [11].

• Lichen planus. Oral lichen planus is a long-term immune condition of the lining of the mouth. It affects about 1% of people worldwide, more often after age 40 [12]. The classic form is a lace-like pattern of white lines (reticular), usually on both cheeks, and it often causes no symptoms. Red, eroded (atrophic or erosive) forms are sore, especially with spicy or acidic foods. Biopsy is often needed to confirm the diagnosis and to make sure there is no dysplasia (precancerous change). Lichen planus carries a small risk of cancer developing in the affected area. A meta-analysis of 82 studies (26,742 patients) found a transformation rate of 1.14%, higher with tongue involvement, red or eroded lesions, smoking, alcohol and hepatitis C [13]. A meta-analysis using stricter diagnostic criteria found a lower rate of 0.44% [14]. The true figure probably lies in this range, and periodic examination is advised. Topical corticosteroid gels are the usual first treatment for painful lichen planus. A Cochrane review found they are more likely than placebo to relieve pain, though the evidence is of low certainty [15].

• Pemphigus and pemphigoid. These are autoimmune blistering diseases in which antibodies attack the proteins that hold the lining together. Blisters break quickly in the mouth, so they usually look like raw, painful erosions. Pemphigus vulgaris often begins with painful mouth erosions before the skin is involved [16]. Mucous membrane pemphigoid often affects the gums, giving a red, peeling appearance, and can also scar the eyes, nose, throat and larynx [17]. Both are diagnosed with a biopsy of the tissue next to a lesion, including direct immunofluorescence, along with blood antibody tests [9, 16]. Treatment is usually shared with dermatology. For pemphigus, the antibody medicine rituximab added to corticosteroids now produces complete remission off therapy in about 90% of patients [16].

• Other autoimmune and inflammatory conditions. Sjögren's disease reduces saliva and causes the problems described in section 6. Crohn's disease can cause swollen lips, cobblestone-like swelling of the cheek lining, tag-like folds and aphthous ulcers. These can appear before the bowel disease is diagnosed, and they usually improve when the bowel disease is treated [18]. Sarcoidosis can also involve the mouth and salivary glands [11].

• Diabetes. Diabetes is among the endocrine conditions that can show changes in the mouth [11]. Its link with lichen planus is uncertain. A meta-analysis of 22 studies found conflicting results [19].

• Nutritional deficiencies. Low vitamin B12, folate and iron can cause a smooth, red, sore tongue (atrophic glossitis), mouth burning and recurring ulcers. In a meta-analysis of nine studies, people with recurrent aphthous ulcers were more likely to be low in vitamin B12 (odds ratio 3.75), folic acid (7.55) and ferritin, a measure of iron stores (2.62) [6]. In a Taiwanese series of patients with atrophic glossitis and low B12, 64% were anemic and 55% had antibodies against the stomach cells that absorb B12 (the pattern of pernicious anemia) [20]. Deficiencies of other B vitamins and zinc have also been associated with mouth symptoms [11]. Celiac disease is another cause worth checking. A meta-analysis of 21 studies found recurrent aphthous ulcers in 25% of people with celiac disease, compared with 11% of controls [6].

• Thyroid disease and Parkinson disease. Thyroid disease is another endocrine condition that can affect the mouth, and thyroid function is often checked in people with unexplained burning [11]. Burning mouth is more common in Parkinson disease. In a case-control study of 150 patients and 150 matched controls, it was found in 4.7% of those with Parkinson disease and none of the controls [21]. The evidence for both links is limited.

• Behçet's disease. Behçet's is an inflammation of blood vessels that causes recurring mouth ulcers together with genital ulcers, eye inflammation, skin lesions and sometimes blood vessel or nervous system involvement. Mouth ulcers are usually its first and most constant feature. Under the International Criteria for Behçet's Disease, oral ulcers, genital ulcers and eye lesions each score 2 points, and other features score 1. A total of 4 or more points supports the diagnosis. In 2,556 patients and 1,163 controls, these criteria were about 94% sensitive and 92% specific [22].

2. Infectious causes

Infections are more likely when the normal defenses of the mouth are reduced. This happens when a person is not eating by mouth (NPO), since chewing and swallowing help clean the mouth. It also happens with a dry mouth, dentures, inhaled steroids, antibiotics, diabetes, and with weakened immunity from cancer treatment, transplant medicines or HIV.

• Fungal: "Thrush" (oral candidiasis). Usually caused by Candida albicans, which accounts for about 77% of cases [6]. It appears as white, curd-like patches that wipe off and leave a red base, or as red, sore areas, often under a denture or at the corners of the mouth. Burning and altered taste are common. Thrush is more common with immune suppression (about 35% of people with HIV), dry mouth (odds ratio 3.02) and recent antibiotics [6]. Mild cases are treated with clotrimazole troches or nystatin suspension, and moderate to severe cases with oral fluconazole [23]. Treating the underlying cause, such as cleaning dentures and rinsing after inhaled steroids, helps prevent it from coming back.

• Viral. Herpes simplex virus type 1 causes painful gum and mouth ulcers with fever on first infection, usually in childhood. Afterward it lies dormant in nerves and reactivates as cold sores on the lip or clusters of small ulcers on the gums and hard palate [24]. Early antiviral treatment shortens outbreaks. In two randomized trials, a one-day course of high-dose valacyclovir started at the first tingle shortened healing time and pain compared with placebo [25]. In people with weakened immunity, herpes can cause larger, longer-lasting ulcers anywhere in the mouth. Coxsackie viruses cause hand, foot and mouth disease, with small ulcers in the mouth and a rash on the hands and feet, mainly in young children. Mumps and parvovirus can also cause mouth findings. Viral illnesses usually resolve on their own within one to two weeks.

• Bacterial. Poor oral hygiene and gum disease increase bacteria in the mouth and the risk of ulcers and infection. A pyogenic granuloma is a soft, red, easily bleeding growth, usually on the gums. Despite its name it is not an infection. It is an exaggerated healing response to irritation, often from plaque, tartar, a dental infection, or hormonal changes in pregnancy. It is treated by removing the growth and the source of irritation.

3. Neoplastic causes

Most oral cancers are squamous cell carcinomas that arise from the lining. Less common tumors include minor salivary gland cancers (such as adenocarcinoma), odontogenic tumors growing from the jaw to the surface, lymphoma and mucosal melanoma. A fibroma is a common, harmless, firm lump, usually from repeated cheek or lip biting. Early mouth cancer may be painless. Warning signs include a sore that does not heal, a white or red patch, a lump or thickening, bleeding, numbness, a loose tooth without gum disease, or a neck lump. These are covered in more depth on the oral cavity tumors page.

Some lesions are potentially malignant disorders, meaning they carry an increased risk of cancer developing in that area [26]. The most common is leukoplakia. A 2025 meta-analysis of 55 studies (41,231 patients) found that 6.6% of leukoplakias became cancer. The risk was higher for non-uniform (speckled or nodular) leukoplakia, large lesions, lesions on the side of the tongue (12.7%), smokers, and lesions with dysplasia on biopsy [8]. In a US database study of more than 59,000 patients, the five-year transformation rate for leukoplakia was 15.6% [27]. Erythroplakia is less common but carries a much higher risk. In a University of California, San Francisco cohort, 11 of 22 patients with erythroplakia (50%) developed oral cancer [28]. Estimates vary widely between studies because of differences in definitions, populations and follow-up.

The American Dental Association guideline (2017) concluded that no screening aid, including toluidine blue dye, light-based (autofluorescence) devices or brush cytology, was accurate enough for routine use. For a suspicious lesion, prompt biopsy or referral to a specialist is the single most important step [3]. A 2021 Cochrane review of 63 studies reached the same conclusion: none of these tests can replace a biopsy. Light-based tests, for example, detected most cancers and precancers (87%) but also flagged about half of harmless lesions [4].

4. Trauma

• Mechanical. A sharp or broken tooth, a rough filling, a poorly fitting denture or orthodontic wire can cause a sore at the point of contact. Tori are harmless bony bumps on the palate (torus palatinus) or inside the lower jaw (torus mandibularis). Their thin covering is easily scraped by hard foods. Tongue thrusting, cheek or lip biting, and sucking habits cause sores in a predictable location. A traumatic ulcer should heal within about two weeks once the cause is removed. One that does not heal should be biopsied, because some cancers look like simple trauma [3].

• Thermal. Hot food and drink (the classic "pizza burn" on the palate) and smoke can burn the lining.

• Neuropathy. Reduced sensation, for example from chemotherapy-associated nerve damage, can lead to unnoticed biting and rubbing injuries. Altered sensation after radiation is also common and can persist long after mucositis heals [7].

5. Contact and chemical causes

• Toothpaste, mouthwash and flavorings. It is worth asking whether anything new started shortly before the sores began. Sodium lauryl sulfate (SLS), the foaming agent in most toothpastes, may promote canker sores. In a double-blind crossover trial of 30 people with frequent canker sores, ulcers were significantly more frequent when brushing with an SLS toothpaste than with an SLS-free paste [29]. A larger trial of 90 patients found that SLS-free toothpaste did not reduce the number of ulcers, but they healed faster and hurt less [30]. A systematic review of four trials concluded that SLS-free toothpaste may help, though better trials are needed [31]. Cinnamon flavoring in gum, candy and toothpaste can cause red, white or ulcerated patches, usually on the cheeks and sides of the tongue. In a series of 74 people, all cleared within a week of stopping the cinnamon product [32]. Alcohol-containing mouthwashes can also irritate the lining.

• Spicy and acidic foods. These irritate lining that is already inflamed, but are rarely the main cause.

• Tobacco, nicotine salts and betel nut. Smoking and smokeless tobacco cause white patches and are the leading risk factors for oral cancer. Smoking also raises the cancer risk of leukoplakia and lichen planus [8, 13]. Betel (areca) nut chewing causes oral submucous fibrosis, a stiffening of the lining with a high cancer risk. The five-year transformation rate was 18.6% in one large database study [27]. Nicotine pouches and e-cigarette liquids with nicotine salts are newer exposures, and their long-term effects on the mouth are not yet known.

• Allergy to food or dental materials. Some white or red patches sit directly against an amalgam (silver) filling. These lichenoid contact lesions often improve after the filling is replaced. In a systematic review of 1,158 patients, complete healing after replacement ranged from 37.5% to 100%. Improvement was most likely when the lesion touched the filling, and patch testing was of limited value in predicting who would benefit [33].

6. Xerostomia and altered salivary quality

Xerostomia is the feeling of a dry mouth. About 23% of people worldwide report it [6]. Saliva protects the lining, so a dry mouth leads to soreness, burning, thrush, tooth decay, trouble swallowing and difficulty wearing dentures. More information about the salivary glands is on the salivary gland page.

• Radiation with fields involving the salivary glands. Radiation for head and neck cancer often damages the parotid and submandibular glands. In the PARSPORT randomized trial, radiation shaped to spare the parotid glands (IMRT) reduced moderate to severe dry mouth at 12 months from 74% to 38% [34]. Current guidelines recommend gland-sparing radiation whenever possible [35]. Amifostine, a drug given during radiation, may reduce dry mouth (low-quality evidence), but it has side effects and is used less often now [36]. Pilocarpine tablets can stimulate remaining gland tissue after radiation. In a randomized trial of 207 patients, dryness improved in 44% on 5 mg three times daily, compared with 25% on placebo, with sweating as the main side effect [37]. See the radiation therapy page.

• Chemotherapy. Chemotherapy can thicken and reduce saliva for a time, which adds to the soreness of mucositis.

• Other drugs. Taking more than three medicines a day roughly triples the odds of dry mouth [6]. A systematic review by the World Workshop on Oral Medicine found good evidence that 56 medicines cause salivary dysfunction or dryness [38]. Common culprits include antidepressants (including SSRIs), anticholinergics (such as bladder medicines), antihistamines, diuretics, some blood pressure medicines and opioids.

• Sjögren's disease. This autoimmune condition attacks the salivary and tear glands. It is evaluated with blood tests and sometimes a lip biopsy.

Management includes sipping water, sugar-free gum or lozenges, saliva substitutes, humidifying the bedroom, fluoride for the teeth, and saliva-stimulating medicines when appropriate [6, 35].

7. Other causes

• Radiation mucositis and chemotherapy mucositis. Mucositis develops during or after radiation fields that include the mouth or throat, and with many chemotherapy drugs. Radiation and chemotherapy damage the dividing cells of the lining, which sets off a cascade of inflammation, thinning and finally ulceration [5]. With a typical six- to seven-week course of head and neck radiation, redness appears in the first two to three weeks and progresses to ulcers covered by a whitish membrane as the dose builds. It peaks near the end of treatment, can continue for two to four weeks afterward, and then heals over several weeks. When chemotherapy is given with radiation, mucositis starts earlier, is more severe and lasts longer [7]. In a systematic review of 33 trials (6,181 patients), mucositis occurred in 80% of patients overall. Severe mucositis occurred in 56% of those receiving accelerated radiation and 34% of those receiving standard radiation. It led to hospital admission in 16% and to interruption of radiation in 11% [1]. In a cohort of 204 patients at MD Anderson, 91% developed mucositis and 66% developed severe mucositis, with more severe pain and weight loss [2]. Mucositis is graded on scales such as the World Health Organization scale. Grade 1 is soreness and redness, grade 2 is ulcers with solid food still possible, grade 3 is a liquid diet only, and grade 4 means eating by mouth is not possible. The commonly used scales track one another closely [7, 39]. Prevention and treatment are covered under Magic mouthwash below. Mucositis also makes swallowing painful, which is covered on the swallowing page.

• Atrophic tongue (atrophic glossitis). This is a smooth, red, often sore tongue that has lost its small surface bumps (papillae). It most often reflects iron, B12 or folate deficiency, and sometimes thrush or a dry mouth [11, 20].

• Geographic tongue (benign migratory glossitis). This is a harmless pattern of smooth red patches with white borders that move around the tongue over days to weeks. Most people have no symptoms, but some have sensitivity to spicy or acidic foods. A systematic review found no proven specific treatment for symptomatic cases. Topical corticosteroids and other measures have been tried, with very low-quality evidence [40].

8. Burning mouth syndrome

Burning mouth syndrome is a chronic burning or painful sensation in the mouth, often the tongue, for which no cause can be found on examination or testing. It is defined as a burning felt in the surface of the lining, recurring daily for more than two hours a day for more than three months, in a mouth that looks normal on examination [41]. It affects about 1.7% of the general population and is most common in women over 50 [42]. It is diagnosed only after the causes above, such as thrush, deficiencies, dry mouth, contact allergy and medicines, have been ruled out. It is now thought to be a disorder of the nerves that carry pain and taste signals.

Treatment evidence is limited. A 2016 Cochrane review of 23 trials found very low-quality evidence for every treatment and could not support or refute any of them [43]. A 2023 network meta-analysis of 44 trials found that clonazepam (often dissolved in the mouth and spit out) was the only treatment likely to reduce pain compared with placebo, with moderate certainty [44]. Low-level light therapy and pregabalin showed possible benefit with low certainty, and alpha-lipoic acid has not shown a consistent benefit [43, 44]. Psychological therapy (cognitive behavioral therapy) showed long-term benefit in a single small trial [43].

Magic mouthwash

"Magic mouthwash" is a general name for a mixed rinse made by a pharmacy. Various formulations or recipes are available. They are sometimes used empirically, with ingredients chosen to cover the likely causes. Typical ingredients are a numbing agent (viscous lidocaine), an antihistamine (diphenhydramine) and a coating antacid, with an antifungal (nystatin) added if thrush is considered, or a corticosteroid if inflammation is the main problem. The formulas used in this practice are on the Magic Mouthwash Formulas page.

What the evidence shows

The largest trial of magic mouthwash studied radiation mucositis. The Alliance A221304 trial randomized 275 patients receiving head and neck radiation, with a mucositis pain score of at least 4 out of 10, to a single dose of doxepin rinse, diphenhydramine-lidocaine-antacid rinse (magic mouthwash) or placebo. Over the next four hours, mouth pain fell by 11.6 points with doxepin, 11.7 points with magic mouthwash and 8.7 points with placebo. Both active rinses were statistically better than placebo, but the differences (about 3 points) were slightly below the 3.5-point change the investigators had set as clinically important. The active rinses caused more drowsiness, unpleasant taste and stinging [46]. An accompanying editorial concluded that these rinses give modest, short-term relief and are best used together with other pain control, not in place of it [47]. A small earlier trial in 26 patients found that a 0.2% morphine mouthwash shortened severe pain by 3.5 days compared with magic mouthwash [48]. The international MASCC/ISOO guideline suggests topical morphine rinse for mucositis pain during chemoradiation [49]. Evidence for magic mouthwash in conditions other than mucositis is limited, and its use there is based on clinical experience.

Preventing and treating mucositis from cancer treatment

The MASCC/ISOO clinical practice guideline (2020) is the main evidence-based guide [50]. For people receiving radiation to the head and neck, it supports the following.

• Basic oral care. Combined oral care protocols, including a dental evaluation before treatment, careful brushing and flossing, and bland rinses throughout treatment, are suggested for prevention [45, 50].

• Photobiomodulation. This is low-level laser therapy applied inside the mouth. It is recommended for prevention during head and neck radiation, with or without chemotherapy [50, 51]. A meta-analysis of 14 randomized trials (869 patients) found that it reduced severe mucositis by about half (risk ratio 0.45 by the end of treatment) and reduced pain [52].

• Benzydamine rinse. This anti-inflammatory rinse is recommended for prevention with moderate-dose radiation (under 50 Gy) and suggested with chemoradiation [50, 53]. In the main randomized trial, it reduced redness and ulceration by about 30% compared with placebo and delayed the need for pain medicines. It did not help with accelerated radiation schedules [54]. Benzydamine is not approved for mucositis in the United States [7].

• Honey and oral glutamine. Honey is suggested with radiation or chemoradiation, and glutamine by mouth with chemoradiation, based on lower levels of evidence. Glutamine given by vein is recommended against [50, 55].

• Not recommended. Chlorhexidine mouthwash is not recommended to prevent radiation mucositis [7, 50].

Ice chips (oral cryotherapy) are recommended with certain chemotherapy, such as bolus 5-fluorouracil and high-dose melphalan, but not for radiation [50]. Palifermin, a growth factor given by vein, reduced severe mucositis from 98% to 63% in patients receiving high-dose chemotherapy and total-body irradiation before a stem cell transplant for blood cancers [10]. It is not used routinely for head and neck cancer. Severe mucositis is associated with more pain, weight loss and opioid use, so rinses are usually combined with regular pain medicine [2, 50]. See also the radiation therapy and chemotherapy and immunotherapy pages.

Summary

• Most mouth sores are harmless and heal within two weeks. Common causes are injury, canker sores, thrush, viral infections and reactions to products or medicines.

• The mouth can reflect conditions elsewhere in the body, including lichen planus, blistering diseases, Crohn's disease, Behçet's disease and vitamin or iron deficiency. Blood tests and sometimes a biopsy help find them.

• A white, red or ulcerated area that does not heal within about two weeks needs a biopsy. Screening lights, dyes and brushes do not replace one.

• Leukoplakia and especially erythroplakia carry a meaningful risk of becoming cancer. Lichen planus carries a small risk. Tobacco use raises the risk in all of these.

• Dry mouth, often from medicines or radiation, makes the lining fragile. Gland-sparing radiation reduces it.

• Mucositis affects most people having head and neck radiation. Basic oral care, photobiomodulation and benzydamine help prevent it, and rinses and pain medicines help control it.

• Magic mouthwash gives modest, short-term relief and is best used as one part of care.

References

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Learning Center Main Index:

Tumors (benign and malignant/cancerous):

general tumor information, thyroid, parathyroid, skin, neck, lymphatics, oropharynx, larynx (voice box), salivary gland, nose and sinus, oral cavity (mouth and lips), nasopharynx, hypopharynx, radiation therapy, chemotherapy and immunotherapy, gastric feeding tube, central line

Nose and Sinus:

rhinoplasty (functional and cosmetic), sinusitis, breathing

Ear:

hearing, infections, dizziness, pressure, tinnitus