Objective: To study the expression of tumor-associated glycoprotein 72 (TAG72) and glucose-regulated protein 94 (GRP94) and their clinicopathological significances in benign and malignant lesions of the stomach. Methods: The conventional paraffin-embedded sections were prepared from the surgical resected or gastroscopic biopsy specimens that included 49 cases of gastric cancer tissues, 20 cases of peritumoral tissues, 36 cases of metastastic foci in lymph nodes and 80 cases of benign lesions of different types. Immunohistochemical staining was performed to determine the expression level of TAG72 and GRP94. Results: The positive rates of TAG72 and GRP94 expression in gastric cancer were significantly higher than those in peritumoral tissues and different types of benign lesions (P＜0.05 or P＜0.01). The peritumoral tissues and benign lesions with positive expression of TAG72 and/or GRP94 all showed mild to severe degrees atypical hyperplasia of mucosal epithelia. The positive rates of TAG72 and GRP94 expression showed no significant differences between the primary foci and the corresponding metastatic foci in lymph nodes (both P＞0.05). The positive rates of TAG72 and GRP94 expression in the cases of tumor invasion depth T1+T2 and no metastasis to regional lymph nodes or distant organs were significantly lower than those of invasion depth T3+T4, metastasis of regional lymph nodes or distant organs (P＜0.05 or P＜0.01). The positive rates of TAG72 and GRP94 expression in the cases of histological grade II and N1 lymph nodes involvement were lower than those of histological grade III+IV and N2+N3 lymph nodes involvement, but both had no significant difference (both P＞0.05). Conclusions: The expression level of TAG72 and/or GRP94 may play a promoting role in the occurrence, development and biological behaviors of gastric cancer, and the positive expression of TAG72 and/or GRP94 in gastric cancer patients predicts a poor prognosis.