Cancer of the pancreas is a genetic disease. The most common genetic alterations identified to date in pancreatic cancer are activation of the K-ras oncogene (approximately 90%) and inactivation of the p16 (approximately 95%), p53 (50% to 75%), DPC4 (55%), and BRCA2 (7%) tumor suppressor genes. An understanding of the molecular genetics of carcinoma of the pancreas is important because it may help explain the aggregation of pancreatic cancer in families and may lead to the development of novel tests to detect early cancers. For example, the aggregation of pancreatic cancer in some families has been shown to result from inherited mutations in cancer-causing genes, and genetic alterations shed from pancreatic cancers have been detected in stool specimens. In addition, we believe that an improved knowledge of the molecular genetics of pancreatic cancer will lead to the development of a new generation of rational and more effective treatments.