Abstract: Objective: To detect the expression of genes Her-2/neu,DPC4 and p16 in pancreatic carcinomas and investigate the role of thier alterations in tumorigenesis and progression of pancreatic carcinomas. Methods We studied the immunohistochemical markers Her-2/neu,DPC4 and p16 in 34 adenocarcinomas and 12 nonmalignant specimens of the pancreas，and the relationship between DPC4 alterations and various clinicopathological parameters was evaluated by statistics. Results There was a significant difference between normal pancreatic tissues and benign pancreatic lesions and primary pancreatic carcinomas for frequency of Her-2/neu expression and loss of p16 expression (P<0.05). The levels of loss of DPC4 expression were increased in primary pancreatic carcinoma in comparison to nonmalignant specimens of the pancreas. The frequency of loss of DPC4 expression was greater in primary pancreatic carcinomas with poor-differentiation than with good and moderate- differentiation (P<0.05).The frequency of Her-2/neu expression and loss of p16 expression was greater in primary pancreatic carcinomas with lymph node-positive than with lymph node-negative (P<0.05)； Followed in TNM staging, the levels of Her-2/neu expression were significantly decreased (P<0.05)，and the frequency of loss of p16 expression was also significantly increased (P<0.05). The expression of Her-2/neu was correlated with p16 (P<0.05); the expression of Her-2/neu was correlated with DPC4 (P<0.05); the expression of p16 was correlated with DPC4 (P<0.01). Conclusion These data suggest that the abnormal expression of Her-2/neu, DPC4 and p16 was helpful for predicting the prognosis. The expression of p16 and DPC4 had an impact on the development of pancreatic carcinoma.