Type 2 human immunodeficiency virus (HIV-2), originally confined to West Africa, has lately appeared with increasing frequency in Europe. Oral lesions affect a large proportion of patients with AIDS. Hairy leucoplakia (HL), a clinical expression of Epstein-Barr virus (EBV), is a lesion of the oral mucosa (usually the lateral margin of the tongue) that is observed in patients who are immunocompromised due to HIV or, more rarely, due to immunosuppressive medication or other causes. We review the definition, clinical signs, histopathology, diagnosis, prognosis and treatment of HL, and report the (to our knowledge) first detailed description of an HIV-2-seropositive patient with HL, which affected the lateral and dorsal tongue and was the first clinical sign of HIV infection (this patient was at that time only the second native Spaniard in whom unique HIV-2 infection had been detected). EBV detection and subtyping by in situ hybridization and polymerase chain reaction were performed in paraffin-embedded tissue from the HL lesion of the dorsal tongue; EBV-1 and EBV-2 were detected by the latter technique.