As reported, ~85% of CRC cases are thought to evolve from conventional adenomas with the acquisition of mutations in APC, SMAD4, TP53, KRAS, or PI3KCA, resulting in Wnt-β-catenin and TGF-β pathway activation; this process is referred to as the adenoma-to-carcinoma sequence. The gene discussed is SMAD4; the disease is carcinoma.