RCAS1 (receptor-binding cancer antigen expressed on SiSo cells) inhibits the in vitro growth of receptor-expressing cells and induces apoptosis, which may contribute to the ability of tumor cells to evade host immune surveillance. In this study, we investigated RCAS1 expression in gastric cancer and precancerous lesions by immunohistochemical means. We then analyzed the relationship between RCAS1 expression and clinicopathological variables, and examined whether RCAS1 expression is associated with infiltration of tumor-infiltrating lymphocytes (TILs) and apoptosis of TILs. Of 54 gastric cancers analyzed, RCAS1 expression was positive in 52 (96%) of them. The expression pattern of RCAS1 in gastric cancer cells could be classified as granular staining either enriched in the glandular side of the cytoplasm with polarity (P pattern) or scattered diffusely in the cytoplasm and on the cell membranes (D pattern). Nineteen of 39 intestinal-type carcinomas (49%) showed the P pattern, and all of 13 diffuse type carcinomas (100%) showed the D pattern. In contrast, all RCAS1-positive specimens of gastric adenoma and metaplastic mucosa were of the P pattern. The D pattern of gastric cancers was more frequently recognized in carcinomas with large size (P < 0.01), in those with regional lymph node metastasis (P < 0.05) and in those that had invaded beyond the submucosa (P < 0.01), compared with the P pattern. On the same sections, significantly less TILs were identified in RCAS1-positive areas than RCAS1-negative areas. Furthermore, the rate of apoptosis of TILs was significantly higher in RCAS1-positive areas than in RCAS1-negative areas. The expression and distribution of RCAS1 may be involved in malignant transformation, tumor progression, histological type and tumor escape from host immune surveillance in gastric cancer.