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To review data demonstrating the prognostic and predictive impact of microsatellite instability (MSI) in human colon carcinomas.MSI is a molecular marker of defective DNA mismatch repair that is detected in approximately 15% of sporadic colon cancers. Most, but not all retrospective studies, have shown that colon cancers with MSI have better stage-adjusted survival rates compared with non-MSI tumors. Furthermore, analyses of colon cancers from participants in randomized adjuvant therapy trials have suggested that MSI tumors do not benefit from treatment with 5-fluorouracil. Recent studies, including a pooled analysis, validate prior data demonstrating the prognostic and predictive impact of MSI status in colon cancer.MSI is a molecular marker that can provide valuable prognostic and predictive information in colon cancer patients. In the appropriate clinical setting, MSI data can be used in clinical decision-making. Specifically, the favorable outcome of stage II colon cancers with MSI indicates that such patients should not receive adjuvant chemotherapy. Although data for stage III colon cancers with MSI suggest a lack of benefit from 5-fluorouracil alone, the benefit of the current standard treatment, 5-fluorouracil, leucovorin, and oxaliplatin, in this subgroup remains unknown and awaits further study.