The mechanism by which TGF-β signaling switches from anti- to pro-oncogenic activity remains poorly understood, but genetic alterations of TGF-β signaling components (e.g., TβRI and TβRII) or the absence of Smad4-mediated signal transduction are features of genetically heterogeneous CRC [9–11]. The gene discussed is TGFBR1; the disease is colorectal carcinoma.