MLH1 and hereditary neoplastic syndrome: Microsatellite instability (MSI) is caused by a defect in the DNA mismatch repair (MMR) system, which can occur sporadically by epigenetic alterations in the MLH1 gene, or in the context of the most common inherited cancer syndrome, named Lynch syndrome, by mutational inactivation of one of the four MMR genes (MLH1, MSH2, MSH6 and PMS2).1 As a consequence, mismatches occurring during DNA replication cannot be corrected, and small insertion/deletion mutations accumulate at short repetitive stretches called microsatellites.