To clarify the significance of p53 mutations in liver metastasis of colorectal carcinogenesis, the characteristics of p53 mutations from 51 liver metastases and 76 primary invasive carcinomas without liver metastasis (Dukes' A, B and C) were compared. The frequency of tumors with p53 mutations was 61% (31 out of 51) in the liver metastases, and 51% (39 out of 76) in the primary carcinomas without liver metastasis. Approximately 90% of the informative cases having p53 mutation showed 17pLOH. Mutations detected within exons 4-10 of the p53 gene included missense, nonsense, frameshift, inframe deletion, and inframe insertion mutations. Out of the tumors with p53 mutations, we found that the percentage of tumors with protein-truncating mutations (nonsense and frameshift mutations) was extremely higher in liver metastases (16 out of 31, 52%) than in primary carcinomas without liver metastasis (5 out of 39, 13%) (P=0.0005). The present results suggest that protein-truncating mutations of the p53 gene are more relevant than missense mutations as one of the prognostic factors in liver metastasis of colorectal carcinomas.