Pancreatic adenocarcinomas are known to have a high incidence of K-ras gene mutation. We summarize our efforts to detect micrometastases through a search for mutated K-ras oncogene in liver tissues, peritoneal washings, para-aortic lymph nodes, and perioperative peripheral blood. Two-stage polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analysis were used to detect K-ras oncogene mutations at codon 12. Our results suggest that PCR/RFLP analysis is potentially highly sensitive for the detection of micrometastases in various tissues and might be of value in the diagnosis, treatment and follow-up of metastases in other organs with pancreatic adenocarcinoma. (C) 1998 Wiley-Liss, Inc.