The presence of APC mutations as an alternative to CTNNB1 mutations in some POLE‐mutant endometrial cancers is an exemplar, and there are likely to be others, such as NF1 and RB1 mutations in endometrial cancer and atypical (Q61P, K117 N, and A146T) KRAS mutations in colorectal cancer. The gene discussed is POLE; the disease is colorectal cancer.