Among individuals who met Medicare testing criteria, the most commonly affected gene was MSH2 followed by MSH6 and MLH1. Although MSH2 and MLH1 are highly penetrant and expected to represent a large proportion of classic LS families, the larger number of MSH6 variants identified in this study could be due to testing of women with personal history of endometrial cancer. The gene discussed is MSH6; the disease is endometrial cancer.