We reported, in Cancer Genetics and Cytogenetics in 2003 [1], the identification of germline mutations of the hMSH2 gene in two out of 11 cases of microsatellite instability (MSI)-positive endometrial cancer that did not meet the New Amsterdam Criteria. In that report, there were mutations of ATG to ATA (Met to Ile) at codon 688 in case 1 and CTT to TTT at codon 390 in case 11. These germline mutations are registered in the genetic mutation database “Human Genome Database (HGMD)” (http://archive.uwcm. ac.uk/uwcm/mg/hgmd0.htm), and similar germline mutations have been previously reported in hereditary nonpolyposis colorectal cancer (HNPCC) cases [2,3]. In addition, these mutations are not currently registered in the database for genetic polymorphisms. The mutation at codon 688 of the hMSH2 gene, identified in case 1, was detected in HNPCC cases among Japanese patients by Nomura et al. [4], who reported that codon 688 of the hMSH2 gene was wild-type in 100 control cases among the Japanese population. To examine whether these mutations were functional, we further analyzed germline mutations of the hMSH2 gene in 179 healthy Japanese individuals. Under informed consent, DNA was extracted from leukocytes of these healthy individuals, and germline mutations were analyzed as previously reported [4]. Mutation at codon 688 of the hMSH2 gene was identified in three out of 179 cases, an overall rate of 1.67% (95% confidence interval (CI): 0.23–3.3%). In addition, mutation of codon 390 was detected at an even higher rate (7%) among these healthy individuals. The present data show that these missense mutations at codons 688 and 390 of the hMSH2 gene were polymorphic DNA variants. The possibility that the missense mutation at codon 688 of the hMSH2 gene is a functional mutation still remains to be elucidated, and we are not able to decide