Diagnosis is usually made on the clinical appearance without the need for a tissue biopsy. However, when biopsies have been taken, the histologic appearance is one of marked elongation and hyperparakeratosis of the filiform papillae and numerous bacteria growing on the epithelial surface.

Hairy tongue may be confused with hairy leukoplakia, however the latter usually occurs on the sides of the tongue and is associated with an opportunistic infection with Epstein–Barr virus on a background immunocompromise (almost always human immunodeficiency virus infection but rarely other conditions which suppress the immune system).

Hairy tongue (lingua villosa) refers to a marked accumulation of keratin on the filiform papillae on the dorsal surface of the tongue, giving a hair-like appearance. Black tongue (lengua negra) refers to a black discoloration of the tongue, which may or may not be associated with hairy tongue. However, the elongated papillae of hairy tongue usually develop discoloration due to growth of pigment producing bacteria and staining from food. Hence the term black hairy tongue, although hairy tongue may also be discolored yellow or brown. Transient, surface discoloration that is not associated with hairy tongue can be brushed off. Drug-induced black hairy tongue specifically refers to BHT that develops because of medication.

Good oral hygiene (thorough tooth brushing and flossing and regular professional cleaning and examination) may be helpful to prevent these disorders. Drinking plenty of water and the production of enough saliva, aid in the reduction of bacterial growth. Minimizing irritants or injury in the mouth when possible can aid in the prevention of glossitis. Avoiding excessive use of any food or substance that irritates the mouth or tongue may also help.

The diagnosis is usually made on the clinical appearance alone, and biopsy is not usually indicated. The histologic appearance is one of marked hyperparakeratosis producing a ragged surface with many projections of keratin. Typically there is superficial colonization by bacteria. There may be vacuolated cells in the upper portion of the prickle cell layer. There is a similarity between this appearance and that of hairy leukoplakia, linea alba and leukoedema. In people with human immunodeficiency virus, who are at higher risk of oral hairy leukoplakia, a tissue biopsy may be required to differentiate between this and frictional keratosis from cheek and tongue chewing.

The differential diagnosis includes oral lichen planus, erythematous candidiasis, leukoplakia, lupus erythematosus, glossitis, and chemical burns. Atrophic glossitis is usually distinguished from benign migratory glossitis on the basis of the migrating pattern of the lesions and the presence of a whitish border, features which are not present in atrophic glossitis, which instead shows lesions which enlarge rather than migrate. Rarely, blood tests may be required to distinguish from glossitis associated with anemia or other nutritional deficiencies. Since the appearance and the history of the condition (i.e. migrating areas of depapillation) are so striking, there is rarely any need for biopsy. When biopsy is taken, the histopathologic appearance is quite similar to psoriasis:

- Hyperparakeratosis.

- Acanthosis.

- Subepithelial T lymphocyte inflammatory infiltrate.

- Migration of neutrophilic granulocytes into the epithelial layer, which may create superficial microabscesses, similar to the Munro's microabscesses described in pustular psoriasis.

The diagnosis is usually made on the clinical appearance, and tissue biopsy is not usually needed. The histologic picture is one of superficial candidal hyphal infiltration and a polymorphonuclear leukocytic inflammatory infiltrate present in the epithelium. The rete ridges are elongated and hyperplastic (pseudoepitheliomatous hyperplasia, which may be mistaken for carcinoma).

Tissue biopsy is usually indicated to rule out other causes of white patches and also to enable a detailed histologic examination to grade the presence of any epithelial dysplasia. This is an indicator of malignant potential and usually determines the management and recall interval. The sites of a leukoplakia lesion that are preferentially biopsied are the areas that show induration (hardening) and erythroplasia (redness), and erosive or ulcerated areas. These areas are more likely to show any dysplasia than homogenous white areas.

Brush biopsy/exfoliative cytology is an alternative to incisional biopsy, where a stiff brush is scraped against the lining of the mouth to remove a sample of cells. This is then made into a smear which can be examined microscopically. Sometimes the biopsy site can be selected with adjunct methods which aim to highlight areas of dysplasia. Toluidine blue staining, where the dye is preferentially retained by dysplastic tissue, is sometimes used, but there is high false positive rate. Other methods involve the use of illuminescence, relying on either the property of normal autoflorescent molecules in mucosa such as collagen and keratin which is lost from areas of dysplasia or carcinoma under blue light, or by initially staining of the mucosa with toluidine blue or dilute acetic acid and examination under white light.

Strawberry tongue (also called raspberry tongue), refers to glossitis which manifests with hyperplastic (enlarged) fungiform papillae, giving the appearance of a strawberry. White strawberry tongue is where there is a white coating on the tongue through which the hyperplastic fungiform papillae protrude. Red strawberry tongue is where the white coating is lost and a dark red, erythematous surface is revealed, interspaced with the hyperplastic fungiform papillae. White strawberry tongue is seen in early scarlet fever (a systemic infection of group A β- hemolytic streptococci), and red strawberry tongue occurs later, after 4–5 days. Strawberry tongue is also seen in Kawasaki disease (a vasculitic disorder primarily occurring in children under 5), and toxic shock syndrome. It may mimic other types of glossitis or Vitamin B12 deficiency.

Chronic ulcerative stomatitis is a recently discovered condition with specific immunopathologic features. It is characterized by erosions and ulcerations which relapse and remit. Lesions are located on the buccal mucosa (inside of the cheeks) or on the gingiva (gums). The condition resembles Oral lichen planus when biopsied.

The diagnosis is made with Immunofluorescence techniques, which shows circulating and tissue-bound autoantibodies (particulate stratified squamous-epithelium-specific antinuclear antibody) to DeltaNp63alpha protein, a normal component of the epithelium. Treatment is with hydroxychloroquine.

The white lesion cannot be wiped away, unlike some other common oral white lesions, e.g. pseudomembranous candidiasis, and this may aid in the diagnosis. Diagnosis of OHL is mainly clinical, but can be supported by proof of EBV in the lesion (achieved by in situ hybridization, polymerase chain reaction, immunohistochemistry, Southern blotting, or electron microscopy) and HIV serotesting. When clinical appearance alone is used to diagnose OHL, there is a false positive rate of 17% compared to more objective methods. The appearance of OHL in a person who is known to be infected with HIV does not usually require further diagnostic tests as the association is well known. OHL in persons with no known cause of immunocompromise usually triggers investigations to look for an underlying cause. If tissue biopsy is carried out, the histopathologic appearance is of hyperlastic and parakeratinized epithelium, with "balloon cells" (lightly staining cells) in the upper stratum spinosum and "nuclear beading" in the superficial layers (scattered cells with peripheral margination of chromatin and clear nuclei, created by displacement of chromatin to the peripheral nucleus by EBV replication). Candida usually is seen growing in the parakeratin layer, but there are no normal inflammatory reactions to this in the tissues. There is no dysplasia (OHL is not a premalignant lesion).

The diagnosis can typically be made from the clinical appearance alone, but not always. As candidiasis can be variable in appearance, and present with white, red or combined white and red lesions, the differential diagnosis can be extensive. In pseudomembraneous candidiasis, the membranous slough can be wiped away to reveal an erythematous surface underneath. This is helpful in distinguishing pseudomembraneous candidiasis from other white lesions in the mouth that cannot be wiped away, such as lichen planus, oral hairy leukoplakia. Erythematous candidiasis can mimic geographic tongue. Erythematous candidiasis usually has a diffuse border that helps distinguish it from erythroplakia, which normally has a sharply defined border.

Special investigations to detect the presence of candida species include oral swabs, oral rinse or oral smears. Smears are collected by gentle scraping of the lesion with a spatula or tongue blade and the resulting debris directly applied to a glass slide. Oral swabs are taken if culture is required. Some recommend that swabs be taken from 3 different oral sites. Oral rinse involves rinsing the mouth with phosphate-buffered saline for 1 minute and then spitting the solution into a vessel that examined in a pathology laboratory. Oral rinse technique can distinguish between commensal candidal carriage and candidiasis. If candidal leukoplakia is suspected, a biopsy may be indicated. Smears and biopsies are usually stained with periodic acid-Schiff, which stains carbohydrates in fungal cell walls in magenta. Gram staining is also used as Candida stains are strongly Gram positive.

Sometimes an underlying medical condition is sought, and this may include blood tests for full blood count and hematinics.

If a biopsy is taken, the histopathologic appearance can be variable depending upon the clinical type of candidiasis. Pseudomembranous candidiasis shows hyperplastic epithelium with a superficial parakeratotic desquamating (i.e., separating) layer. Hyphae penetrate to the depth of the stratum spinosum, and appear as weakly basophilic structures. Polymorphonuclear cells also infiltrate the epithelium, and chronic inflammatory cells infiltrate the lamina propria.

Atrophic candidiasis appears as thin, atrophic epithelium, which is non-keratinized. Hyphae are sparse, and inflammatory cell infiltration of the epithelium and the lamina propria. In essence, atrophic candidiasis appears like pseudomembranous candidiasis without the superficial desquamating layer.

Hyperplastic candidiasis is variable. Usually there is hyperplastic and acanthotic epithelium with parakeratosis. There is an inflammatory cell infiltrate and hyphae are visible. Unlike other forms of candidiasis, hyperplastic candidiasis may show dysplasia.

There are no specific treatments for this problem, other than using ice or numbing medicines to ease the pain.

The condition may disappear over time, but it is impossible to predict if or when this may happen.

The lesions are harmless, and no treatment is indicated beyond reassurance, unless the person requests it. The most common and simple treatment is construction of a specially made acrylic prosthesis that covers the biting surfaces of the teeth and protects the cheek, tongue and labial mucosa (an occlusal splint). This is either employed in the short term as a habit breaking intention, or more permanently (e.g. wearing the prosthesis each night during sleep). Psychological intervention is also reported, but does not appear to be beneficial.

Leukoplakia has a wide range of possible histologic appearances. The degree of hyperkeratosis, epithelial thickness (acanthosis/), dysplasia and inflammatory cell infiltration in the underlying lamina propria are variable. In mucous membranes, hyperkeratosis can be defined as "an increase in the thickness of the keratin layer of the epithelium, or the presence of such a layer in a site where none would normally be expected." In leukoplakia, the hyperkeratosis varies in thickness, and may be either ortho- or para-keratosis, (depending upon whether cell nuclei are lost or retained in the superficial layers respectively), or a mixture of both in different areas of the lesion.

The epithelium may show hypertrophy (e.g. acanthosis) or atrophy. Red areas within leukoplakia represent atrophic or immature epithelium which has lost the ability to keratinize. The transition between the lesion and normal surrounding mucosa may be well demarcated, or poorly defined. Melanin, a pigment naturally produced in oral mucosa, can leak from cells and give a grey color to some leukoplakia lesions.

Hyperkeratosis and altered epithelial thickness may be the only histologic features of a leukoplakia lesion, but some show dysplasia. The word "dysplasia" generally means "abnormal growth", and specifically in the context of oral red or white lesions refers to microscopic changes ("cellular atypia") in the mucosa that indicate a risk of malignant transformation. When dysplasia is present, there is generally an inflammatory cell infiltration in the lamina propria. The following are commonly cited as being possible features of epithelial dysplasia in leukoplakia specimens:

- Cellular pleomorphism, in which cells are of abnormal and different shapes.

- Nuclear atypia, in which the nuclei of cells varies in size, any may be increased in size relative to the cytoplasm, shape, and may stain more intensely. There may also be more prominent nucleoli.

- Increased number of cells seen undergoing mitosis, including both normal and abnormal mitoses. Abnormal mitosis may be abnormally located, e.g. occurring in suprabasal cells (cell layers more superficial to the basal cell layer) or of abnormal form, e.g. "tri-radiate mitoses" (a cell splitting into 3 daughter cells rather than only 2)

- Loss the normal organization of the epithelial layers. The distinction between the epithelial layers may be lost. Normally stratified squamous epithelium shows progressive changes in the form of cells from the basal to the superficial layers, with cells becoming more flat ("squames") towards the surface as a continuous maturation process. In dysplastic epithelium, cells may become vertically orientated rather than becoming flat towards the surface.

- There may be abnormal keratinization, where keratin is formed below the normal keratin layer. This can occur in individual cells or groups of cells, forming an intraepithelial keratin pearl. There may be an increase in number of basal cells, and they may lose their cellular orientation (losing their polarity and long axis).

- Alteration of the normal epithelial-connective tissue architecture - the rete pegs may become "drop shaped". wider at their base than more superficially.

Generally dysplasia is subjectively graded by pathologists into mild, moderate or severe dysplasia. This requires experience as it is a difficult skill to learn. It has been shown that there is high degree of inter-observer variation and poor reproducibility in how dysplasia is graded. Severe dysplasia is synonymous with the term carcinoma in situ, denoting the presence of neoplastic cells which have not yet penetrated the basement membrane and invaded other tissues.

Treatment may involve smoking cessation and prescription of topical or systemic antifungal medication. Usually the mucosal changes resolve with antifungal therapy, but sometimes the lesion is resistant to complete resolution.

Oral and maxillofacial pathology, previously termed oral pathology, is a speciality involved with the diagnosis and study of the causes and effects of diseases affecting the oral and maxillofacial regions (i.e. the mouth, the jaws and the face). It can be considered a speciality of dentistry and pathology. Oral pathology is a closely allied speciality with oral and maxillofacial surgery and oral medicine.

The clinical evaluation and diagnosis of oral mucosal diseases are in the scope of oral & maxillofacial pathology specialists and oral medicine practitioners, both disciplines of dentistry.

When a microscopic evaluation is needed, a biopsy is taken, and microscopically observed by a pathologist. The American Dental Association uses the term oral and maxillofacial pathology, and describes it as "the specialty of dentistry and pathology which deals with the nature, identification, and management of diseases affecting the oral and maxillofacial regions. It is a science that investigates the causes, processes and effects of these diseases."

In some parts of the world, oral and maxillofacial pathologists take on responsibilities in forensic odontology.

The oral lesion itself is benign and self-limiting, however this may not necessarily be the case for the underlying cause of immunocompromise. For instance, OHL with HIV/AIDS is a predictor of bad prognosis, (i.e. severe immunosuppression and advanced disease).

Terms such as "plasma cell gingivostomatitis", "atypical gingivostomatitis" and "idiopathic gingivostomatitis" are sometimes a synonym for plasma cell gingivitis, or specifically to refer to a severe form of plasma cell gingivitis.

The severity of oral candidiasis is subject to great variability from one person to another and in the same person from one occasion to the next. The prognosis of such infection is usually excellent after the application of topical or systemic treatments. However, oral candidiasis can be recurrent. Individuals continue to be at risk of the condition if underlying factors such as reduced salivary flow rate or immunosuppression are not rectifiable.

Candidiasis can be a marker for underlying disease, so the overall prognosis may also be dependent upon this. For example, a transient erythematous candidiasis that developed after antiobiotic therapy usually resolves after antibiotics are stopped (but not always immediately), and therefore carries an excellent prognosis—but candidiasis may occasionally be a herald of a more sinister undiagnosed pathology, such as HIV/AIDS or leukemia.

It is possible for candidiasis to spread to/from the mouth, from sites such as the pharynx, esophagus, lungs, liver, anogenital region, skin or the nails. The spread of oral candidiasis to other sites usually occurs in debilitated individuals. It is also possible that candidiasis is spread by sexual contact. Rarely, a superficial candidal infection such as oral candidiasis can cause invasive candidiasis, and even prove fatal. The observation that Candida species are normally harmless commensals on the one hand, but are also occasionally capable of causing fatal invasive candidiases has led to the description "Dr Jekyll and Mr Hyde".

The role of thrush in the hospital and ventilated patients is not entirely clear however there is a theoretical risk of positive interaction of candida with topical bacteria that could increase the risk for Ventilator Associated Pneumonia and other diseases.

This is a rare inflammatory condition of the minor salivary glands, usually in the lower lip, which appears swollen and everted. There may also be ulceration, crusting, abscesses, and sinus tracts. It is an acquired disorder, but the cause is uncertain. Suspected causes include sunlight, tobacco, syphilis, poor oral hygiene and genetic factors. The openings of the minor salivary gland ducts become inflamed and dilated, and there may be mucopurulent discharge from the ducts. A previous classification suggested dividing cheilitis into 3 types based on severity, with the later stages involving secondary infection with bacteria, and increased ulceration, suppuration and swelling: Type 1, Simple; Type 2, Superficial suppurative ("Baelz's disease"); and Type 3, Deep suppurative ("cheilitis glandularis epostemetosa"). Cheilitis glandularis usually occurs in middle-aged and elderly males, and it carries a risk of malignant transformation to squamous cell carcinoma (18% to 35%). Preventative treatment such as vermilionectomy ("lip shave") is therefore the treatment of choice.

BMS is a diagnosis of exclusion, i.e. all other explanations for the symptoms are ruled out before the diagnosis is made. There are no clinically useful investigations that would help to support a diagnosis of BMS (by definition all tests would have normal results), but blood tests and / or urinalysis may be useful to rule out anemia, deficiency states, hypothyroidism and diabetes. Investigation of a dry mouth symptom may involve sialometry, which objectively determines if there is any reduction of the salivary flow rate (hyposalivation). Oral candidiasis can be tested for with use of a swabs, smears, an oral rinse or saliva samples. It has been suggested that allergy testing ("e.g.", patch test) is inappropriate in the absence of a clear history and clinical signs in people with a burning sensation in the mouth. The diagnosis of a people with a burning symptom may also involve psychologic screening e.g. depression questionnaires.

The second edition of the International Classification of Headache Disorders lists diagnostic criteria for "Glossodynia and Sore Mouth":

Tongue lesions are very common. For example, in the United States one estimated point prevalence was 15.5% in adults. Tongue lesions are more common in persons who wear dentures and tobacco users. The most common tongue conditions are geographic tongue, followed by fissured tongue and hairy tongue.

The name "lie bumps" is a result of a myth that telling lies would cause them. However, very little has been written about this condition in scientific articles or textbooks and scientific studies have failed to produce a definite cause. Possible causes include: "stress, gastrointestinal upset, menstruation, acidic or sour food, smoking, and local trauma" (direct physical irritation) of the tongue. Lie bumps are often caused by the taste bud(s) splitting.

These bumps are small, white bumps on the base of the tongue. They are likely to be the result of transient lingual papillitis (TLP). This condition is limited to the upper (dorsal) surface of the tongue, affecting some of the tiny bumps on the tongue known as the fungiform papillae, what we commonly call the "taste buds."

TLP is a harmless problem. These bumps can become notably red or white and are quite tender for up to several days. While the cause of TLP is not known with certainty, most experts feel that local accidental trauma (rubbing, scraping or biting) is a major factor; however, contact reactions to things like certain foods have also been suggested. Lie bumps are not contagious and the discomfort is relatively minor. Typically these lesions heal within a few days with no treatment, though a doctor may refer a patient to an oral pathologist in prolonged cases.

There are many oral and maxillofacial pathologies which are not fully understood.

- Burning mouth syndrome (BMS) is a disorder where there is a burning sensation in the mouth that has no identifiable medical or dental cause. The disorder can affect anyone but tends to occur most often in middle aged women. BMS has been hypothesized to be linked to a variety of factors such as the menopause, dry mouth (xerostomia) and allergies. BMS usually lasts for several years before disappearing for unknown reasons. Other features of this disorder include anxiety, depression and social isolation. There is no cure for this disorder and treatment includes use of hydrating agents, pain medications, vitamin supplements or the usage of antidepressants.

- Aphthous stomatitis is a condition where ulcers (canker sores) appear on the inside of the mouth, lips and on tongue. Most small canker sores disappear within 10–14 days. Canker sores are most common in young and middle aged individuals. Sometimes individuals with allergies are more prone to these sores. Besides an awkward sensation, these sores can also cause pain or tingling or a burning sensation. Unlike herpes sores, canker sores are always found inside the mouth and are usually less painful. Good oral hygiene does help but sometime one may have to use a topical corticosteroid.

- Migratory stomatitis is a condition that involves the tongue and other oral mucosa. The common migratory glossitis (geographic tongue) affects the anterior two thirds of the dorsal and lateral tongue mucosa of 1% to 2.5% of the population, with one report of up to 12.7% of the population. The tongue is often fissured, especially. in elderly individuals. In the American population, a lower prevalence was reported among Mexican Americans (compared with Caucasians and African Americans) and cigarette smokers. When other oral mucosa, beside the dorsal and lateral tongue, are involved, the term migratory stomatitis (or ectopic geographic tongue) is preferred. In this condition, lesions infrequently involve also the ventral tongue and buccal or labial mucosa. They are rarely reported on the soft palate and floor of the mouth.