Although it cannot be excluded that loss of Smad4 function underlies intestinal tumour formation in these animals through Tgf-β/BMP downstream effectors independent of Wnt signaling, the histology and molecular features of the Apc+/1572T/Smad4+/Sad GI polyps strongly suggest that the further increase of Wnt/β-catenin signaling conferred by the Smad4 mutation in the Apc-mutant background results in intestinal tumours in the compound mice without apparently affecting the mammary cancer phenotype. This evidence concerns the gene SMAD4 and intestinal neoplasm.