Records of 105 patients with central nervous system (CNS) lymphoma were analyzed in order to better define the incidence, setting, and management of CNS lymphoma and the role for CNS prophylaxis. Survival was best for patient under 30 years of age treated with whole-brain irradiation and intrathecal (IT) chemotherapy whose CNS involvement was an isolated event (median survival time, 1.8 years). Survival was worst for patients over 30 years of age whose CNS invasion occurred at a time of progressive systemic lymphoma (median time ten weeks if treated with whole-brain irradiation with or without IT chemotherapy). The risk of CNS invasion was greatest for those with lymphoblastic lymphoma. Among patients with Stage IIE, III, or IV histiocytic lymphoma, the risk of CNS involvement was greatest for those with progressive or relapsing disease or involvement of the testes, peripheral blood, or epidural space of the spinal cord.