The p53 gene is known to be one of the frequently altered tumor suppressor genes, involved in the oncogenesis of a wide spectrum of human malignant tumors. We investigated mutational events of the p53 gene in 18 clinically untreated prostate cancers. Direct sequencing analysis demonstrated that 1 of 18 cases harbored point mutation in the highly conserved transcript region. The case showed CAT at codon 273 instead of wild-type CGT, substituting the encoded amino acid form histidine to arginine. The case had previously revealed homozygous loci on 17p, including the p53 locus, by restriction fragment length polymorphism analysis. The other 17 cases harbored neither mutation nor small deletion. It is concluded that point mutation of the p53 gene is a infrequent event in the oncogenesis of untreated prostate cancer.