We report the first case of Cryptococcus neoformans infection in a HIV patient in Estonia. Systemic cryptococcosis and AIDS were diagnosed in an 18-year-old female post mortem in May 2003. The opportunistic fungal pathogen was isolated from the patient’s blood. For diagnostic purposes, testing of the CSF or serum for the polysaccharide antigen of Cryptococcus neoformans by latex agglutination or ELISA is highly recommended. For patients with immunosupression and signs of meningeal irritation, direct microscopic examination of the cerebrospinal fluid can be used for rapid diagnosis. Treatment guidelines for cryptococcosis are discussed. In Estonia, the number of HIV positive patients is high and increase in different opportunistic infections is predictable.