BACKGROUND/AIMS: Despite considerable advances in imaging technique and diagnostic tool, early diagnosis of pancreatic adenocarcinoma and differential diagnosis from chronic pancreatitis remain elusive. Mutations in K-ras oncogene at codon I are detected at 75 100% in pancreatic carcinornas and are believed to be a critical event in early stage of oncogenesis. As most pancreatic cancers are adenocarcinoma derived from the ductal epithelium, proliferating cancer cells ot the ductal nest may puss into pancreatic juice. Therefore the author attempted to detect K-ras mutations in DVA ohtained from pure pancreatic juice collected endoscopically as a novel noninvasive diagnostic method to detect pancreatic carcinoma. METHODS: K-ras mutations were examined using the two-step polymerase chain reaction(PCR) combined with restriction enzyme digestion, followed by single strand conformation polymorphism(SSCP) analysis and direct sequencing. RESULTS: Specific mutations of K-ras gene at codon 12 were found in seven of nine(77.8%) chict cell carcinonas by enriched PCR and SSCP method. K-ras mutations were not detected in the pancreatic juice frorn IO healthy control subjects, five patients with chronic pancreatitis, or two patients with mucinous cystadenoma. The most frequently observed type of mutations at codon 12 was G - C transversion(GCiT - CGT), resulting in alteration of glycine to arginine. There was no apparent correlation between the location, size or stage of the tumor and the detection rate of K-ras mutations at codon 12. CONCLUSIONS: Detection of K-ras mutation at codon 12 in pancreatic juice is a highly specific diagnostic modality for pancreatic ductal carcinoma and may be valuable for early detection of pancreatic carcinoma and differentiation between chronic pancreatitis and carcinoma.