PURPOSE: Microsatellite instability-high (MSI-H) colorectal cancer (CRC) displays a well-described distinct phenotype, but the true biological significance of MSI-low (L) is still uncertain. To clarify the significance of this MSI-L, we studied the differences between patients with CRC with MSI-H, MSI-L, and microsatellite stability (MSS). METHODS: A total of 723 consecutive patients (429 males and 294 females) who had undergone resections between September 2002 and August 2007 were studied. We analyzed the clinicopathological features, the MSI statuses, and the prognoses of the 723 CRC patients. RESULTS: MSI-H was observed in 54 (7.5%), MSI-L in 27 (3.7%), and MSS in 642 (88.8%) of the 723 colorectal cancer patients. MSI-L and MSS CRC share similar clinicopathological features. A univariate analysis showed no significant differences in overall survival between MSI-L, MSS, and MSI-H. In the multivariate Cox regression analysis, MSI-L was significantly (P=0.036) associated with poorer prognosis compared with MSS tumors, after adjustment for factors previous shown to be associated with the survival based on potentially relevant variables. CONCLUSION: In conclusion, the current study showed no difference in the clinicopathological features of MSI-L versus MSS CRCs. However, in the multivariate analysis, patients with MSI-L CRCs had significantly poorer overall survival. Finally, these findings support the existence of MSI-L CRCs as a distinct category. Thus, further studies are required to explore possible reasons for the adverse prognosis associated with MSI-L cancers.