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The natural history of pancreatic ductal adenocarcinoma makes it one of the most malignant human diseases. Unknown etiology, lack of early symptoms, explosive outcome, short survival, and resistance to therapy are hallmarks of this cancer. Although surgery has been shown to be an effective therapeutic approach, the inevitable tendency for recurrence, even after apparently curative operation, has remained a mystery. Ironically, the reasons for this recurrence, which usually leads to the death of the patient within 1 or 2 years after surgery, have not been a focus of research. Several studies highlighting this problem and the possible explanations have been performed by Japanese investigators.