Primary central nervous system lymphomas (CNSL) are uncommon neoplasms accounting for about 1% of primary brain tumors. Patients with congenital or acquired immunodeficiencies including AIDS patients and transplant recipients represent the main high-risk population for CNSL occurrence. An important point emerging from the literature is that CNSL incidence has dramatically increased during the last years not only in HIV infected patients by virtue of the AIDS epidemic spread, but also for unclear reasons in immunologically normal persons. Although c-myc oncogene activation and Epstein-Barr virus infection are considered to play a role in CNSL development, the peculiar tendency of these lymphomas to occur and remain inside the CNS is not well understood and may involve putative CNS binding molecules carried by lymphocytes. The clinical presentation is characterized by a great variety of neurological disorders. Radiological features consist of hyperdense homogeneous deposits within the subcortical white matter with a pattern of marked enhancement after injection of contrast material. The tumor masses are usually ill-defined and multicentric. Although all cytological types can be observed, the most common types belong to the high-grade category of non-Hodgkin's lymphoma. Monoclonal antibodies reactive with formalin-fixed, paraffin-embedded sections can be used in conjunction with stereotactic needle biopsy to provide accurate immunological characterization of CNSL. The large majority of CNSL is of B-cell origin but T-cell lymphomas seem at the present time less exceptional than previously thought. Although radiotherapy and chemotherapy can increase length of survival, the prognosis of CNS remains dramatically poor, the shortest survival being observed in AIDS patients.