Abstract: Objective: To observe the expression of epithelial cell adhesion molecule (Ep-CAM) and heparanase (Hpa) in primary gallbladder carcinoma,and to investigate their role in the genesis and development of primary gallbladder carcinoma. Methods: Ep-CAM protein and Hpa protein were determined in 50 cases of primary gallbladder carcinoma,20 cases of gallbladder adenoma and 20 cases of chronic cholecystitis using immunohistochemistry EliVision^TM plus staining method. Results: The positive rate of Ep-CAM expression in gallbladder carcinoma was higher than that in cholecystitis (P < 0.05). The positive rate of Hpa expression in gallbladder carcinoma was higher than that in gallbladder adenoma and cholecystitis (P < 0.05). The positive rate of Ep-CAM expression and Hpa in gallbladder carcinoma was related with the Nevin stages (P < 0.05 and P < 0.01). The median survival time of the tumor patients with or without overexpression of Ep-CAM was 13 and 24 months, respectively. Conclusions: The expression of Ep-CAM and Hpa may play an important part in the genesis and progression of gallbladder carcinoma,and may act as a marker for gallbladder carcinoma metastasis. Ep-CAM can be used as a prognostic marker for patients with advanced gallbladder carcinoma.