Mutations of the p53 gene result in increased stability and accumulation of the p53 protein, permitting p53 protein detection by immunohistochemical techniques. We have utilized immunohistochemistry to examine accumulation of the p53 protein at various stages of progression in prostatic adenocarcinomas. p53 protein accumulation was detected using the monoclonal antibody BP53-12-1 in 3 of 28 (11%) localized prostatic adenocarcinomas, and in prostatic intraepithelial neoplasia (PIN) in 1 of 16 (6%) specimens. In contrast, p53 protein was detected in 9 of 16 (56%) primary prostatic adenocarcinomas that were metastatic (stage D), and in 10 of 18 (56%) matching metastases to lymph nodes from these same patients. Thus, we observed a higher incidence of p53 protein accumulation in matching primary and metastatic lesions of patients with stage D adenocarcinoma than in localized (nonmetastatic) adenocarcinomas. We also found that an antigen retrieval solution (ARS) aided in the detection of p53 protein accumulation in prostatic adenocarcinomas. The results indicate that accumulation of p53 protein occurs prior to metastasis, and identifies a subclass of prostatic adenocarcinomas that express a high potential for metastasis.