Many studies have investigated the expression of c-met and c-erbB2 protein in human gastric adenocarcinomas, but the expression of gastrin protein in human gastric cancer and the relationship between gastrin and c-met are unknown. We have constructed a tissue microarray containing 408 formalin-fixed and paraffin-embedded human tissue blocks, including tissues containing intestinal metaplasia (IM, n=72) and primary tumors (n=232), as well as normal gastric mucosa (n=104) from patients with gastric cancer. Immunohistochemistry (IHC) was used for detecting gastrin, c-met and c-erbB2 proteins. Gastrin was detected in 13.5% (7/52) and c-met in 15.3% (11/72) of IM cases. In gastric carcinomas, 48.4% (103/213) of cases expressed gastrin, 68.8% (148/215) expressed c-met, and 5.5% (11/200) expressed c-erbB2. Gastrin and c-met protein expression were significantly higher in gastric tumor tissue than in IM (P<0.0001). Overexpression of c-erbB2 protein was detected in gastric carcinomas but not in normal gastric mucosa (P<0.05). Expression of gastrin and c-met protein was associated (P<0.01), but no significant difference was found on the changes of gastrin, c-met and c-erbB2 expression in gastric cancer with tumor stage, grade of differentiation or tumor type. These results indicate that gastrin and c-met play a role in the early process during malignant transformation of the gastric mucosa.