The expression of the tumour suppressor gene p53 was analyzed in a variety of human solid tumours by immunohistochemistry and direct DNA sequencing. Positive nuclear staining using a panel of anti-p53 antibodies was used to select tumours for further genetic analysis. Using PCR amplification followed by immobilization onto magnetic beads and direct sequencing, we sequenced exons 5-9 of the p53 gene from 9 melanomas, 8 nasopharyngeal carcinomas, 16 sporadic breast carcinomas and 11 patients from familial breast cancer families. No sequence alterations of the p53 gene were detected in either the melanoma or nasopharyngeal tumours and only 19% of the primary breast carcinomas showed a variant band indicative of a mutation. Our results indicate firstly that p53 mutations are not generally involved in the tumour types studied and secondly the data emphasize the disparity encountered when attempting to correlate p53 immunohistochemical positivity with mutations within the p53 gene.