Loss‐of‐function mutations in RNF43 induce activation of Wnt ligand‐dependent Wnt/β‐catenin signaling through stabilization of the Frizzled receptor, which is often found in microsatellite instability (MSI)‐type colorectal cancer (CRC) that develops from sessile serrated adenomas. The gene discussed is RNF43; the disease is adenoma.