The caudal-related homeodomain protein2 (CDX2) is a transcription factor shown to play a role in the development of small and large intestine in mammals and in the differentiation of intestinal epithelial cells. It has been shown that CDX2 protein detection by IHC correlates with RNA transcript levels. In studies using 745 cancers from many anatomic sites, colonic adenocarcinomas demonstrated strong staining in 90% of the cases, while adenocarcinomas of the stomach, esophagus and ovary showed extensive staining in only 30% of the cases. Stains of CDX2 and Villin are useful markers in differential diagnosis of bladder adenocarcinoma and secondary colorectal adenocarcinoma.