The purpose of this study was to elucidate microsatellite instability (MSI) and p53 expression for each tumor in cases with sporadic synchronous multiple colorectal cancers. Twenty-nine patients with sporadic synchronous multiple colorectal cancer were examined. There were sixty-five tumors, all of which indicated adenocarcinoma histopathologically. The MSI was assessed using six microsatellite markers (BAT26, BAT40, D2S136, D5S346, D11S922, D17S250). Tumors with two or more positive loci were determined to be MSI-H (high-frequency MSI), tumors with one positive locus were designated as MSI-L (low-frequency MSI) and tumors lacking apparent instability were designated as MSS (microsatellite stable). In addition, overexpression of p53 protein was examined using immunohistochemical (IHC) methods for each tumor. The DO-7 monoclonal antibody was used in the IHC assessments. The following results were obtained: i) there were nine patients who indicated MSI-H at the first tumor (1-H group) and 20 patients who had MSI-L or MSS at the first tumor (1-LS group). ii) The ratio of cases that indicated MSI-H at the second tumor and beyond in the 1-H group was 88.9% (8/9), which was significantly higher than that of the 1-LS group (30.0%, 6/20) (p=0.0021). iii) The frequency of cases with the right-sided colon in the 1-H group (61.9%) was significantly higher than that of the 1-LS group (27.3%) (p=0.0073). In addition, a significant difference was noted in terms of the ratio of cases with poorly differentiated adenocarcinoma or mucinous carcinoma between the two groups [1-H group (19.0%) vs 1-LS group (0%), p=0.0028]. Furthermore, no distinct relationship between MSI status and p53 overexpression was obtained. In conclusion, we think that sporadic synchronous multiple colorectal cancers should be divided into two types; one type that indicates multiple occurrence of MSI-H consecutive tumors and another type that shows multiple occurrence irrespective of MSI.