[6] Risk factors for formation inside the mouth include smoking, chewing tobacco, excessive alcohol, and use of betel nuts.

[4][6] Other conditions that can appear similar include yeast infections, lichen planus, and keratosis due to repeated minor trauma.

[4] If abnormal cells are present or the lesion is small surgical removal is often recommended; otherwise close follow up at three to six month intervals may be sufficient.

[2][21] Erythroleukoplakia (also termed speckled leukoplakia, erythroleukoplasia or leukoerythroplasia) is a non-homogeneous lesion of mixed white (keratotic) and red (atrophic) color.

[23] However, some sources use this term to refer to leukoplakia lesions that become colonized secondarily by Candida species, thereby distinguishing it from hyperplastic candidiasis.

It is now rare, but when syphilis was more common, this white patch usually appeared on the top surface of the tongue and carried a high risk of cancerous changes.

[25] In the context of lesions of the mucous membrane lining of the bladder, leukoplakia is a historic term for a visualized white patch which histologically represents keratinization in an area of squamous metaplasia.

[32] Cigarette smoking may produce a diffuse leukoplakia of the buccal mucosa, lips, tongue and rarely the floor of mouth.

[29] 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.

[29] DNA damage was measured in oral leukoplakia patients using single cell gel electrophoresis (also called the “comet assay”) applied to peripheral blood samples.

[35] In another study, DNA damage, also measured by the comet assay, was found to be greater in oral leukoplakia and squamous-cell carcinoma than in control subjects.

[29] In 1984 an international symposium agreed upon the following definition: "a whitish patch or plaque, which cannot be characterized clinically or pathologically as any other disease, and is not associated with any physical or chemical agent except the use of tobacco.

[29] At a second international symposium held in 1994, it was argued that whilst tobacco was a likely causative factor in the development of leukoplakia, some white patches could be linked directly to the local effects of tobacco by virtue of their disappearance following smoking cessation, suggesting that this kind of white patch represents a reactive lesion to local tissue irritation rather than a lesion caused by carcinogens in cigarette smoke, and could be better termed to reflect this etiology, e.g. smokers' keratosis.

[30] Tissue biopsy is usually indicated[5] to rule out other causes of white patches and also to enable a detailed histologic examination to grade the presence of any epithelial dysplasia.

[3] Other methods involve the use of luminescence, 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.

"[22] 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.

Melanin, a pigment naturally produced in oral mucosa, can leak from cells and give a grey color to some leukoplakia lesions.

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.

[39] 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.

[3] In keratosis, the thickened keratin layer absorbs water from saliva in the mouth and appears white in comparison with normal mucosa.

Normal oral mucosa is a red-pink color due to the underlying vasculature in the lamina propria showing through the thin layer of epithelium.

A frictional keratosis will generally be adjacent to a sharp surface such as a broken tooth or rough area on a denture and will disappear when the causative factor is removed.

A chemical burn has a clear history of placing an aspirin tablet (or other caustic substance such as eugenol) against the mucosa in an attempt to relieve toothache.

Developmental white patches usually are present from birth or become apparent earlier in life, whilst leukoplakia generally affects middle aged or elderly people.

[9] Regardless of the treatment used, a diagnosis of leukoplakia almost always leads to a recommendation that possible causative factors such as smoking and alcohol consumption be stopped,[40] and also involves long term review of the lesion,[40] to detect any malignant change early and thereby improve the prognosis significantly.

[2] Since smoking and alcohol consumption also places individuals at higher risk of tumors occurring in the respiratory tract and pharynx, "red flag" symptoms (e.g. hemoptysis - coughing blood) often trigger medical investigation by other specialties.

Even if the lesion is completely removed, long term review is still usually indicated since leukoplakia can recur, especially if predisposing factors such as smoking are not stopped.

[2] Some of this research is carried out based upon the hypothesis that antioxidant nutrients, vitamins and cell growth suppressor proteins (e.g. p53) are antagonistic to oncogenesis.

[30] It is now thought that this white lesion on the tongue represented syphilitic glossitis,[30] a condition not included in the modern definitions of oral leukoplakia.

[48] According to one source from 1961, leukoplakia can occur on multiple different mucous membranes of the body, including in the urinary tract, rectum, vagina, uterus, vulva, paranasal sinuses, gallbladder, esophagus, eardrums, and pharynx.