Pancreatic cancer is a common malignant neoplasm in digestive tract, which is of unknown etiology as yet. Recent advances in molecular oncology have provided explanations at the DNA level that multiple genetic changes contribute to pancreatic cancer development, in which the p16 locus of tumor tissue is nearly always altered. This tumor suppressor gene, located on chromosome 9p21, encodes for a protein that is involved in cell cycle regulation. Alterations of the p16 gene for the carcinogenesis in the pancreas involve different molecular mechanisms, including deletion, mutation or methylation. As recent anecdotal case reports that pancreatic cancer aggregates in some families, the patterns of inheritance of pancreatic cancer were studied utilizing molecular genetic techniques for some kindreds which exhibit aggregation of the cancer, and germline mutation in p16 gene have been demonstrated to predispose to pancreatic cancer. In addition, the anticancer effects of exogenous p16 gene have been shown by introduction of it into human pancreatic tumor cell lines. At the present time it is uncertain whether the p16 gene provides clinically prognostic information. Microsatellite instability was observed at one or more loci in a number of pancreatic cancers, but pancreatic cancers with mismatch repair deficiency may have an improved prognosis.