Infiltrating ductal adenocarcinoma of the pancreas is a real enigma. On one hand, it is one of the most deadly of all of the solid malignancies. On the other hand, the neoplastic glands can be remarkably well-differentiated, and it can be difficult to distinguish between a reactive non-neoplastic gland and a gland of invasive adenocarcinoma. In this review, we will present diagnostic criteria that one can "hang your hat on" when establishing the diagnosis of infiltrating ductal adenocarcinoma of the pancreas. We will also review clinically important features of the disease, and, with the impending incorporation of molecular genetics into everyday practice, we will emphasize clinical applications of cancer genetics.