Long‐term CWP232291 (small‐molecule Wnt inhibitor) treatment of Villin‐Cre;Smad4F/F;Trp53F/F mice suppressed intestinal tumorigenesis and progression. CWP232291 treatment downregulated cancer stem cell (CSC) tumor markers including CD133, Lgr‐5, and Sca‐1. This evidence concerns the gene LGR5 and neoplasm.