PURPOSE: Colorectal cancers that display high-degree microsatellite instability are associated with an improved prognosis and evidence of an activated host immune response. Molecular analyses have suggested that heat shock proteins, a family of proteins that have key immunologic functions, are upregulated in these cancers. We aimed to explore the expression of heat shock proteins 70 and 110 and their relationship to microsatellite instability, survival, and other clinicopathologic parameters. METHODS: Twenty-six colorectal cancers that displayed microsatellite instability were matched by age, stage, and site in the colorectum to 26 microsatellite-stable cancers. Immunohistochemistry was used to detect expression of both markers. RESULTS: The microsatellite-unstable group showed significantly higher expression of heat shock protein 70 than the microsatellite-stable group (P = 0.006), and patients undergoing curative resections for unstable cancers had improved prognosis compared with their stable counterparts (P = 0.026). Significantly, in a multivariate survival analysis, low or absent heat shock protein 70 expression was independently associated with a poor outcome (P = 0.001). CONCLUSIONS:Heat shock protein 70 has known functions that promote antitumor immune responses. Its overexpression in colorectal cancers with microsatellite instability may be pivotal to explaining these tumors’ enhanced immunogenicity and improved prognosis. PURPOSE: Colorectal cancers that display high-degree microsatellite instability are associated with an improved prognosis and evidence of an activated host immune response. Molecular analyses have suggested that heat shock proteins, a family of proteins that have key immunologic functions, are upregulated in these cancers . We aim to explore the expression of heat shock proteins 70 and 110 and their relationship to microsatellite instability, survival, and other clinicopathologic parameters. METHODS: Twenty-six colorectal cancers that displayed microsatellite instability were matched by age, stage, and site in the Colorectum to 26 microsatellite-stable cancers. Immunohistochemistry was used to detect expression of both markers. RESULTS: The microsatellite-unstable group with significantly higher expression of heat shock protein 70 than the microsatellite-stable group (P = 0.006), and patients undergoing curative Resections for unstable cancers had improved experience compared with th Eir stable counterparts (P = 0.026). Significantly, in a multivariate survival analysis, low or absent heat shock protein 70 expression was independently associated with a poor outcome (P = 0.001). CONCLUSIONS: Heat shock protein 70 has known functions that promote antitumor Immune responses. Its overexpression in colorectal cancers with microsatellite instability may be pivotal to explaining these tumors’ enhanced immunogenicity and improved prognosis.