Our case, however, is notable for being among a handful of cases of POLE-mutated endometrial and colon cancer that responded dramatically to the immune checkpoint blockade in the context of mutations in the exonuclease proofreading domain of POLE leading to a tumor mutational burden greater than 100 mutations per megabase [32,33,34,35]. The gene discussed is POLE; the disease is malignant colon neoplasm.