p53 is a tumor suppressor gene whose protein product is overexpressed in several human tumors. In this study we used a monoclonal antibody (DO7) direct against p53 and a previously described antigen retrieval methodology to examine p53 expression in 27 cases of microinvasive squamous cell carcinoma of the skin and in 10 cases of Bowen's disease. Immunohistochemical studies were performed on formalin-fixed, paraffin-embedded tissue sections that had been microwave-heated to improve antigenicity. Positive nuclear staining for p53 was observed in 23 of 27 (85%) cases of microinvasive squamous cell carcinoma and in five of 10 (50%) cases Bowen's disease. With the exception of occasional focal positive staining of basal layer cells, no p53 immunoreactivity was observed in normal skin. Our results demonstrate that increased expression of the p53 protein is a common finding in both in situ and microinvasive squamous cell carcinoma of the skin, and they suggest that loss of normal p53 tumor suppressor activity may be an important mechanism of oncogenesis in these neoplasms.