Abstract: New methods of screening for compounds for treating colon cancer are described. Using microarray expression profiling, molecular evidence was obtained supporting lack of differentiation as the mechanism for development of colon polyps and tumors. An absence of retinoic acid (RA) response genes from neoplastic tissue colon tissues was observed. The absence of RA response genes was paralleled by the lack of expression of retinol dehydrogenase 5 and a novel retinol dehydrogenase homolog, RDHL. RDHL expression is highly restricted to normal colon and the colon specific transcription factors, cdx1 and cdx2 can regulate RDHL. Additionally, re-introduction of APC leads to re-expression of RDHL.