A case is reported of a primary central nervous system lymphoma in a heterosexual patient affected by acquired immunodeficiency syndrome. Because of the rarity and the aggressive diagnostic procedures, pre-mortem diagnosis is seldom established. This radiosensitive tumor, however, often contains monoclonal immunoglobulin productive cells and shows, at CT-scan, a multicentric arrangement. On this basis, a careful analysis of the cerebrospinal fluid and CT-scan may offer a possible mean of earlier diagnosis and improve the survival of these patients.