The first studies on mutations in the MLH6 gene indicated that the clinical phenotype of affected families differed from that of individuals with the classical Lynch syndrome caused by mutations in MLH1 and MSH2. Its penetrance seems to be lower, although endometrial cancer is probably the most important clinical manifestation in women who carry a mutation in MLH6. Moreover, mutations in MLH6 have a low incidence of microsatellite instability and preferentially occur in mononucleotide sequences.30 This evidence concerns the gene MSH2 and Lynch syndrome.