Screening for Lynch syndrome (LS) in colorectal cancer (CRC) and endometrial cancer (EC) patients generally involves immunohistochemical staining of the mismatch repair (MMR) proteins. In case of MLH1 protein loss, MLH1 promotor hypermethylation (MLH1-PM) testing is performed to indirectly distinguish constitutional MLH1 variants from somatic epimutations. However, in recent years a growing number of studies have reported that MLH1-PM and pathogenic constitutional MMR variants are not …