The involvement of p53 mutations in prostate cancers in Japan was investigated. To evaluate any possible clinicopathological significance, p53 mutations in 40 samples from 36 Japanese prostate cancers of different stages (five cases of latent tumors, three of stage A cancers, 10 of stage B, five of stage C and 13 of stage D), including four lymph node metastases of stage D cases, were examined by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis and sequencing. Mutations were detected in five of 40 samples (12.5%); four were in primary cancers and the other in a lymph node metastasis from one of them. All mutation-positive cases were in stage D, and the mutation frequency in stage D cases was 31%. This result indicates that p53 mutations may play a role in the progression of a subgroup of prostate cancers in Japanese, as observed for Americans and Europeans. However, a difference was noted between Japanese and Americans in the p53 mutational spectrum (at CpG site), presumably arising from variation in the underlying etiologic factors.