BACKGROUND/AIMS: In order to identify microsatellite instability (MSI), the test based on the polymerase chain reaction (PCR) can be used. However, PCR is not routinely performed in all hospital laboratories. Recently, immunohistochemistry (IHC) for MLH1 and MSH2 proteins has been reported as a rapid and useful method for MSI. However, the efficacy of IHC in the detection of the MSI has not been well established. The aim of this study was to evaluate the usefulness of IHC in the detection of the MSI by comparing it with the test results using PCR in colorectal cancer (CRC). METHODS: Paraffin-embedded normal and tumor tissues from seventy-five patients who underwent surgical resection of CRC were used. Abnormal expression of MLH1 and MSH2 protein was determined by IHC using MLH1 and MSH2 antibodies. Normal and tumor DNAs were obtained from thirty CRC tissues that showed abnormal expression of MLH1 and MSH2 proteins by IHC. The MSI status was confirmed by PCR using five markers. RESULTS: Thirty tumors showed abnormal expression of MLH1 and MSH2 proteins by IHC, but only three tumors out of them were confirmed to have MSI by PCR. CONCLUSIONS: This result suggests that IHC with MLH1 and MSH2 antibodies does not seem to be a useful method to identify MSI in CRC, therefore PCR is required for detection of the MSI.