Oral hairy leukoplakia is a new clinicopathological entity. Little is known about its etiology, pathogenesis and natural history. It is considered a specific marker of HIV infection, although it has been also reported in HIV-negative patients. The etiology appears related to Epstein-Barr virus. Hairy leukoplakia has a characteristic clinical and histopathological aspect, but it is not specific. Because hairy leukoplakia may be easily confused with other lesions of the tongue, the dentist should be very careful in making the final diagnosis. Hairy leukoplakia is usually asymptomatic and treatment is not necessary. In cases of extensive lesions or psychological intolerance of the patient, useful drugs are acyclovir and vitamin A derivatives.