We examined microsatellite instability (MSI) and loss of heterozygosity (LOH) in regions of several important genes in 25 signet-ring cell carcinomas of the stomach. The relationship between microsatellite analysis and DNA ploidy pattern was also investigated. MSI was observed in 15% (2/13) of early carcinomas and in 17% (2/12) of advanced carcinomas. Although LOH in the region of APC gene was found in 16% (4/25) and LOH of p53 was found in 12% (3/25), 15% (2/13) of early carcinomas and 33% (4/12) of advanced carcinomas showed LOH in regions of E-cadherin gene. Cyto-fluorometrical study revealed that 85% (11/13) of early carcinomas were diploid pattern, and aneuploid components were demonstrated in 50% (6/12) of advanced carcinomas. However, no MSI-positive cases contained aneuploid components, and in contrast, all p53-LOH cases contained aneuploid components. Our results suggest that gene abnormalities which have been frequently reported in differentiated adenocarcinomas are rare events in signet-ring cell carcinomas other than those associated with cell adhesion, and that MSI is not related to the occurrence of aneuploid cells.