We report herein a patient with K-ras point mutation at codon 12 that had been detected in pure pancreatic juice (PPJ) obtained 3 yr and 6 months before he was diagnosed with pancreatic cancer (PC). In this 73-yr-old man, PC was diagnosed by ERCP, which showed obstruction of the main pancreatic duct (MPD) at the borderline area between the body and tail of the pancreas. Distal pancreatosplenectomy was performed, and an advanced PC at the tail of the pancreas with a few metastatic nodules in the liver was confirmed. Retrospectively, a K-ras point mutation at codon 12 from GGT (glycine) to GAT (aspartic acid) was detected in the PPJ collected endoscopically 3 yr and 6 months earlier, as well as in the PPJ when PC was diagnosed and in the resected tumor tissue. Reevaluation of pancreatography from the ERCP performed at that time revealed a very mild stenotic lesion of the MPD, speculated to be a PC at a very early stage, at the body-tail border, but it was difficult to diagnose this lesion as a PC, based only on this morphological study. Accordingly, we believe that this is an interesting and valuable clinical case, indicating that K-ras mutation can precede clinical evidence, and its determination in PPJ could be a useful genetic test calling for a careful and extensive clinical investigation for early detection of PC.