In accordance with Knudson’s ‘two hit’ hypothesis, FAP patients with a germline APC mutation have a very high risk to acquire an additional somatic APC mutation mainly in the colorectum, that will eventually lead to the development of multiple adenomas, starting at adolescence, with nearly 100% progression to CRC by the age of 40, if left untreated10–12. Here, APC is linked to colorectal carcinoma.