While MMR genes usually comply with Knudson’s two-hit hypothesis for tumor suppressor genes [69] as evidenced by the lack of the responsible MMR protein in LS-associated cancers (biallelic inactivation), colorectal adenoma development seems possible in LS even if the wild-type allele of the predisposing MMR gene is retained [70, 71]. This evidence concerns the gene MRC1 and colorectal adenoma.