Ependymomas rarely show p53 gene alteration, and the tumorigenic mechanism of ependymomas still remains to be elucidated. We investigated the amplification and overexpression of mdm2 gene, whose product (MDM2) is considered to be one of the major cellular regulators of p53-mediated growth control, in 26 specimens of ependymomas obtained from 20 patients. The majority of the ependymomatous samples (96%) showed at least focal immunopositivity for MDM2; however, only 8% of the samples were immunopositive for p53. mdm2 gene amplification was detected in 35% of the samples by differential polymerase chain reaction, all of which overexpressed MDM2. These results suggest that the amplification and/or overexpression of mdm2 may be one of the major molecular events occurring in the tumorigenesis of ependymomas.