EOMES and cancer: The findings discussed in this article underline the crucial role of TGF-β1/Smad cascade in the maintenance of intestinal homeostasis and indicate that defective function of this signaling pathway, due to gain/loss of function defects in the extracellular/intracellular signal transduction components (e.g., TβR2, Smad7), contribute to trigger and/or amplify detrimental signals in the gut, which may ultimately lead to intestinal inflammation, fibrosis as well as cancer.