Contrary to other human cancers, in CRC almost all mutations that activate WNT/β-catenin signaling are present in genes such as APC, AXIN or CTNB1 (encoding β-catenin), resulting in constitutively active β-catenin to promote TCF/LEF-dependent transcription of WNT target genes irrespective of upstream WNT signals [6]. The gene discussed is APC; the disease is cancer.