Material from paraffin sections of 109 human colorectal carcinomas, mostly obtained at autopsy, was analyzed for the presence of K-ras point mutations at codon 12, position 2. Mutations at this position were found in 23 cases (21.1%). Aneuploid colorectal carcinomas showed a significantly higher prevalence of K-ras point mutations than diploid tumors, suggesting an involvement of ras mutations in the development of aneuploidy. No differences in the prevalence of K-ras mutations were observed with respect to the patients' age, sex and tumor type. In metastases, the type of ras gene mutation was always identical to that of the respective primary tumor. Mutations were not found in metastases from primary tumors devoid of ras mutations. This renders a clonal selection of K-ras mutated cells from a wild-type primary tumor during the metastatic process unlikely. However, nearly twice as many ras gene mutations were seen in metastatic than in non-metastatic primary tumors. © 1992 Wiley-Liss, Inc.