Nodal is a member of the TGF-β family playing important roles in tissue stem cells and cancer stem cells (CSCs), interacting with the co-receptor Cripto-1, as well as with Activin type IB (Alk4) and Activin typeIIreceptors, and maintaining stemness and Notch and Wnt/β-catenin signaling in CSCs. This evidence concerns the gene NODAL and cancer.