Objective To study the expression of p16 and Rb gene in primary gallbladder carcinoma (PGC). MethodsFiftysix cases of PGC and 26 of gallbladder benign lesions were observed by immunohistochemistry (SP). ResultsThe positive rates of p16 and Rb protein in PGC were 46.3% and 71.4% respectively. No association of Rb expression with histological grade, histological type, invasion, metastasis and prognosis was found. There were close correlation between p16 expression and invasion, metastasis as well as prognosis. The inverse correlation of p16 and Rb gene expression in PGC was confirmed. Conclusion The loss of p16 or Rb gene protein is an important molecular event in PGC,and closely related to the block in the negative regulatory pathway of all cell cycle. The detection of p16 protein may be useful in evaluating biological characteristics and prognosis in PGC.