Tobacco smoking or chewing is the most common causative factor, with more than 80% of persons with leukoplakia having a positive smoking history. Smokers are much more likely to suffer from leukoplakia than non-smokers. The size and number of leukoplakia lesions in an individual is also correlated with the level of smoking and how long the habit has lasted for. Other sources argue that there is no evidence for a direct causative link between smoking and oral leukoplakia. Cigarette smoking may produce a diffuse leukoplakia of the buccal mucosa, lips, tongue and rarely the floor of mouth. Reverse smoking, where the lit end of the cigarette is held in the mouth is also associated with mucosal changes. Tobacco chewing, e.g. betel leaf and areca nut, called paan, tends to produce a distinctive white patch in a buccal sulcus termed "tobacco pouch keratosis". In the majority of persons, cessation triggers shrinkage or disappearance of the lesion, usually within the first year after stopping.

Although the synergistic effect of alcohol with smoking in the development of oral cancer is beyond doubt, there is no clear evidence that alcohol is involved in the development of leukoplakia, but it does appear to have some influence. Excessive use of a high alcohol containing mouth wash (> 25%) may cause a grey plaque to form on the buccal mucosa, but these lesions are not considered true leukoplakia.

Erythroplakia has an unknown cause but researchers presume it to be similar to the causes of squamous cell carcinoma. Carcinoma is found in almost 40% of erythroplakia. It is mostly found in elderly men around the ages of 65 - 74. It is commonly associated with smoking.

Alcohol and tobacco use have been described as risk factors.

The exact cause of VIN is unknown. Studies are being done to determine the cause of VIN. The following factors have been associated with VIN:

- HPV (Human Papilloma Virus)

- HSV-2 (Herpes simplex Virus - Type 2)

- Smoking

- Immunosuppression

- Chronic vulvar irritation

- Conditions such as Lichen Sclerosus

Vaccinating girls with HPV vaccine before their initial sexual contact has been claimed to reduce incidence of VIN.

Normally found in children or young adults, a common cause of conjunctival squamous cell papilloma is during childbirth, when the mother passes the virus to her child.

Leukoedema is common. It occurs in about 70-90% of black skinned adults and about 50% of black skinned children. The prevalence in white skinned people is considerably less, but reports range from less than 10% to more than 90%, probably varying depending upon the population studied, and the methods used in the study, e.g. examination conditions and the diagnostic criteria. The ethnic variation may be explained by genetic factors or simply because black skinned people have greater amount of melanin in the mucosa, making it appear darker (termed racial or physiologic pigmentation). This darker mucosa may make the edematous changes more noticeable, whereas in the mucosa of people with lighter skin types leukoedema gives a milder presentation.

The cause is unknown, but it is thought to be caused by intracellular edema of the superficial epithelial cells coupled with retention of superficial parakeratin. Although leukoedema is thought to be a developmental condition, it may be more common and more pronounced in smokers, and becomes less noticeable when smoking is stopped. Smoking cannabis is known to be linked to this condition. It may also develop in areas subjecte to repeat subclinical irritation, caused by low grade irritants such as spices, oral debris or tobacco.

Squamous cell papilloma of the mouth or throat is generally diagnosed in people between the ages of 30 and 50, and is normally found on the inside of the cheek, on the tongue, or inside of lips. Oral papillomas are usually painless, and not treated unless they interfere with eating or are causing pain. They do not generally mutate to cancerous growths, nor do they normally grow or spread. Oral papillomas are most usually a result of the infection with types HPV-6 and HPV-11.

Seborrheic keratosis is the most common benign skin tumor. Incidence increases with age. There is less prevalence in people with darker skin. In large-cohort studies, 100% of the patients over age 50 had at least one seborrheic keratosis. Onset is usually in middle age, although they are common in younger patients too—found in 12% of 15-year-olds to 25-year-olds—making the term "senile keratosis" a misnomer.

Immunoperoxidase stains have identified antigens of the human papillomavirus (HPV) types 6 and 11 in approximately 50% of cases of squamous cell papilloma.

Gardasil 6 is an HPV vaccine aimed at preventing cervical cancers and genital warts. Gardasil is designed to prevent infection with HPV types 16, 18, 6, and 11. HPV types 16 and 18 currently cause about 70% of cervical cancer cases, and also cause some vulvar, vaginal, penile and anal cancers. HPV types 6 and 11 are responsible for 90% of documented cases of genital warts.

Gardasil 9, approved in 2014 protects against HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58.

HPV vaccines do not currently protect against the virus strains responsible for plantar warts (verrucas).

The incidence of the disease is higher in people from certain parts of the world including South-East Asia, South Africa and the Middle East.

There are many other conditions that are similar in appearance and must be ruled out before a diagnosis of erythroplakia is made (see table). Sometimes, a diagnosis is delayed for up to two weeks in order to see if the lesion spontaneously regresses on its own or if another cause can be found. Erythroplakia frequently is associated with dysplasia, and is thus a precancerous lesion.

There is no treatment, but because this is a benign condition with no serious clinical complications, prognosis is excellent.

Smoking, especially heavy smoking, is an important predisposing factor but the reasons for this relationship are unknown. One hypothesis is that cigarette smoke contains nutritional factors for "C. albicans", or that local epithelial alterations occur that facilitate colonization of candida species.

A benign papillomatous tumor is derived from epithelium, with cauliflower-like projections that arise from the mucosal surface.

It may appear white or normal colored. It may be pedunculated or sessile. The average size is between 1–5 cm.

Neither sex is significantly more likely to develop them. The most common site is the palate-uvula area followed by tongue and lips. Durations range from weeks to 10 years.

Malnutrition, whether by malabsorption, or poor diet, especially hematinic deficiencies (iron, vitamin B12, folic acid) can predispose to oral candidiasis, by causing diminished host defense and epithelial integrity. For example, iron deficiency anemia is thought to cause depressed cell-mediated immunity. Some sources state that deficiencies of vitamin A or pyridoxine are also linked.

There is limited evidence that a diet high in carbohydrates predisposes to oral candidiasis. "In vitro" and studies show that Candidal growth, adhesion and biofilm formation is enhanced by the presence of carbohydrates such as glucose, galactose and sucrose.

This variation of normal anatomy is seen in the majority of adults. It is estimated about 80% of people have oral Fordyce spots, but seldom are granules found in large numbers. They are not usually visible in children, and tend to appear at about age 3, then increasing during puberty and become more obvious in later adulthood. They are more prominent in males.

White sponge nevus (WSN, or white sponge naevus, Cannon's disease, hereditary leukokeratosis of mucosa, white sponge nevus of Cannon, familial white folded dysplasia, or oral epithelial nevus), is an autosomal dominant condition of the oral mucosa (the mucous membrane lining of the mouth). It is caused by a mutations in certain genes coding for keratin, which causes a defect in the normal process of keratinization of the mucosa. This results in lesions which are thick, white and velvety on the inside of the cheeks within the mouth. Usually, these lesions are present from birth or develop during childhood. The condition is entirely harmless, and no treatment is required.

Dried products such as paan masala and gutkha have higher concentrations of areca nut and appear to cause the disease. Other causes include:

- Immunological diseases

- Extreme climatic conditions

- Prolonged deficiency to iron and vitamins in the diet

Common seborrheic keratosis (also known as "Basal cell papilloma," and "Solid seborrheic keratosis") is a common benign cutaneous condition characterized by a skin lesion with a dull or lackluster surface.

The virus is relatively hardy and immune to many common disinfectants. Exposure to 90% ethanol for at least 1 minute, 2% glutaraldehyde, 30% Savlon, and/or 1% sodium hypochlorite can disinfect the pathogen.

The virus is resistant to drying and heat, but killed by and ultraviolet radiation.

STK is extremely common among smokeless tobacco users. Given the association with smokeless tobacco use, this condition tends to occur in adults. A national USA survey estimated an overall prevalence of 1.5% of all types of smokeless tobacco lesions, with males affected more commonly than females.

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.