Control of colon cell fate in adenocarcinomas is disrupted, in part, due to aberrant Wnt/β-catenin signaling. The nuclear receptor peroxisome proliferator-activated receptor-γ (PPARγ) has been implicated in the development of colon cancers. In the adenomatous polyposis coli multiple intestinal neoplasia (APC^Min) mouse cancer model, PPARγ expression in the colonic mucosa is markedly altered. In addition, PPARγ protein levels are elevated, possibly through sequestration by activated β-catenin in colon cancer cell lines. Induction of the Wnt/β-catenin pathway by LiCl also elevated PPARγ levels and induced PPARγ-dependent reporter and endogenous target genes. Mechanistically, PPARγ, through interactions with β-catenin and T cell transcription factor (Tcf)-4, may be a determinant of cell fate and is likely a target of the Wnt pathway in cancer cells.