Overexpression of the p53 protein was analyzed in colorectal adenomas, early cancers, advanced cancers and their hepatic metastasis by immunostaining using monoclonal antibody (DO-7). Positive staining for p53 was detected in 8 (22.9%) of 35 adenomas, 19 (82.6%) of 22 early cancers, and 59 (63.2%) of 95 advanced cancers. In adenomas, p53 immunoreactivity for severe dysplasia was higher than that for mild or moderate dysplasia (3/9.33.3% vs 2/16.12.5% or 3/10.33.3%), we found almost the same p53 immunoreactivity both in early cancers in adenoma (7/8.87.5%) and "de novo" cancers without an adenoma component (12/14. 85.7%). In 95 of advanced cancers, we found p53 positive cells in 33 (76.7%) of 43 cases with hepatic metastasis, against 26 (50.0%) of 52 cases without hepatic metastasis and surviving more than 5 years from the colorectal cancer resection. The former group had a significantly higher incidence of p53 overexpression (p < 0.05). In the 33 above mentioned cases, both primary and liver metastatic lesions were p53 positive, and the others were negative in both of them. In this series, it was suggested that p53 had important roles in the colorectal adenoma-carcinoma sequence from adenoma to advanced cancer and its metastatic potential, as well as in "de nove" carcinoma.