Microsatellite instability (MSI) is a hypermutable phenotype that usually arises from either a germline mutation in components of the mismatch repair (MMR) machinery (i.e. hMLH1, MSH2, MSH6 and PMS2) in patients with Lynch syndrome (LS) or somatic hypermethylation of the hMLH1 promoter in sporadic carcinomas. In all colorectal cancers (CRC) is possible to identify the MMR deficiency through protein expression by immunois- tochemistry (IHC). Recently, the predictive role of MMR defi- ciency in reduced chemotherapy benefit and the introduction of universal screening for Lynch syndrome suggest to include MMR testing into routine clinical practice. In this scenario is mandatory to update the minimal requirements for MMR IHC standardiza- tion and evaluation. According to international guidelines, these are the GIPAD and AIFEG suggestions for MMR IHC testing.