Despite uninformative (negative) genetic testing for the LS genes (MSH2, MLH1, MSH6, PMS2) in the patient’s daughter, she was recommended to pursue MSI and IHC for the respective MMR proteins on her CRC to help delineate the tumor phenotype, as a small proportion of such cases can show a defective MMR profile due to acquired (somatic) MMR mutations, or rarely, suggest a germline gene mutation undetectable by standard testing techniques. The gene discussed is MLH1; the disease is colorectal carcinoma.