While it is established that p53 mutation plays a critical role in the carcinogenesis of astrocytic brain tumors, its role remains to be clarified for other types of tumors in the central nervous system (CNS). Using a yeast-based assay which tests the ability of human p53 to activate transcription, we analyzed p53 mutations in 85 non-astrocytic CNS tumors, including 4 benign neuronal tumors (3 central neurocytomas and 1 pineocytoma), 12 primitive neuroectodermal tumors, 14 germ cell tumors (7 germinomas, 7 non-germinomatous tumors), 4 craniopharyngiomas, 14 ependymomas, 22 schwannomas, 10 primary brain lymphomas in immunocompetent patients, and 5 bone tumors of the skull. The only tumors found to contain p53 mutations were 3 malignant lymphomas. The presence of mutations in these cases was confirmed by DNA sequencing. Given the high accuracy and sensitivity of the yeast assay and previous negative results using conventional techniques, this indicates that p53 mutation is a rare event in non-astrocytic CNS tumor types examined here.