B7-H6, a novel member of the B7 family which binds to NKp30 to trigger antitumor NK cell cytotoxicity and cytokine secretion. Recently, B7-H family has been reported to be a negative regulator of the immune response in patients with gastric carcinoma. However, no reports have investigated the clinical significance of B7-H6 expression in human gastric cancer. We present the first study to the clinicopathological and prognostic value of B7-H6 in primary gastric tumors and adjacent non-tumor tissues at the protein level. Here we show that B7-H6 immunoreactivity was expressed in 6/60 (10%) gastric tumors and 8/43 (18.60%) adjacent non-tumor tissues. No statistical difference was found between B7-H6 expression and various prognostic factors; however, B7-H6-positive carcinomas were significantly associated with a higher differentiation (p = 0.047). The survival analysis did not confirm the prognostic significance of B7-H6 expression in gastric cancer patients. Our data suggest that B7-H6, as detected by immunohistochemistry, is of limited value as a prognostic marker for gastric cancer.