BACKGROUND/AIMS: The aims of this study were to evaluate the expression rate of p53 protein and K-ras mutation in pancreatic carcinogenesis, and to determine their clinical significance. METHODS: Specimens were obtained from 26 pancreatitic ductal adenocarcinoma, 12 chronic pancreatitis, and 5 normal pancreas. For the specimens, overexpression of p53 protein was evaluated by immunohistochemical assay, and K-ras mutation was analyzed by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: Immunohistochemical staining for p53 protein was positive in 0% of normal ducts, 25% of chronic pancreatitis, and 61.5% of pancreatic carcinoma. K-ras mutation was positive in 0% of normal ducts, 16.7% of chronic pancreatitis, 76.9% of pancreatic carcinoma. There were no significant correlations between p53 immunoreactivity or K-ras mutation and age, gender, tumor size, histopathological grade, and stage of pancreatic cancer. However, the p53-positive pancreatic cancers showed significantly lower survival rate than a p53-negative tumors (p<0.05). There was no correlation between K-ras multation and survival rates. CONCLUSIONS: The mutations of p53 tumor suppressor gene and K-ras might have important roles in the pancreatic carcinogenesis. The detection of p53 alterations might be useful in the prediction of the patient's prognosis. The genetic alterations of p53 and K-ras are likely to begin in the stage of chronic pancreatitis.