Abstract A subset of gastric cancers shows high microsatellite instability (MSI-H). The reported clinicopathologic features of MSI-H gastric cancers are heterogeneous, and specific factors associated with prognosis have not been identified. We analyzed the clinicopathologic characteristics and prognostic factors in a large series (161 cases) of MSI-H gastric cancers, and compared the results to 315 cases of microsatellite stable or low MSI gastric cancers. The frequency of MSI-H gastric cancers was 9.0% (161/1786). MSI-H gastric cancers have distinct clinicopathologic features including female gender, older age, antral location, protruded gross type (Borrmann typeIand type II), well to moderate differentiation, intestinal type of Lauren classification, expanding type of Ming classification, non signet ring cell component, presence of mucinous component, moderate to severe lymphoid stromal reaction, and lower tumor stage. The MSI-H phenotype was associated with better prognosis (P = .044), and male gender (P = .035, HR: 0.23), intestinal/mixed type of Lauren classification (P <.001, HR: 0.09) and lower tumor stage (1 and 2) (P = .001, HR: 0.08) were independently favorable prognostic factors. With unique clinicopathologic features, the intestinal type MSI-H gastric cancers are associated with good prognosis and can be classified as a different subset of gastric cancers. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 783.