Colorectal cancers with high-frequency microsatellite instability (MSI-H) are known to display striking differences in their clinical and pathological features compared to microsatellite stable (MSS) cancers. Previous studies revealed that MSI-H cancers are more likely to occur in women, irrespective of the higher incidence of colorectal cancer in men. In this study we investigated the gender-specific clinico-pathological features of MSI positive colorectal cancer in Japanese individuals. A series of 478 colorectal carcinomas were collected in an unbiased manner and analyzed for microsatellite instability status. Seven percent, 6% and 87% of tumors showed MSI-H, low-frequency microsatellite instability (MSI-L) and MSS, respectively. A comparison of gender indicated a statistical significance in terms of the distribution of the subsite and age of onset of MSI-H colorectal cancer. In general, MSI-H cancers prone to develop in the proximal colon however, we found that about 36% of MSI-H cancers in men developed in the rectum. These rectal cancers were more likely to have a mucinous component and multiple colorectal cancers including critical lesion. These findings should be useful to find MSI positive rectum cancer.