Because IHC helps to identify the cause of MMR deficiency, we also suggest classifying unusual MMR-D tumors into four sub-groups according to the IHC profile; group 1: isolated loss of PMS2 or MSH6 regardless of the microsatellite status, group 2: classical loss of MLH1/PMS2 or MSH2/MSH6 but with MSI-Low or MSS, group 3: four MMR proteins retained with MSI-H or MSI-Low and group 4: complex loss of MMR protein staining regardless of the microsatellite status. The gene discussed is MSH6; the disease is mismatch repair cancer syndrome 1.