Clinically, in tumors displaying MSI without identified causative mechanism, i.e., absence of pathogenic mutations in hMLH1, hMSH2, hMSH6, or hPMS2 and absence of hMLH1 promoter methylation, the testing for somatic and germline mutations affecting hPMS1 should be considered, particularly in patients with a clinical history suggestive of Lynch syndrome. Here, MSH6 is linked to Lynch syndrome.