APC (adenomatous polyposis coli) is a multi-domain protein regulating numerous cellular functions through interaction with beta-catenin and subsequent inhibition of Wnt signaling. APC germline mutations are associated with familial adenomatous polyposis and somatic mutations with colon, endometrial, non-small cell lung cancer, and breast cancers. Simple APC mutations are seen in about 10% of all cancers. APC is also mutated in more than 40% of colorectal carcinomas and about 7% of skin cancers. Preclinical studies have shown that APC inactivating mutations may predict sensitivity to Tankyrase inhibitors or CTNNB1 inhibitors. Additionally the APC mutation can be used to confirm a colorectal metastasis.