To better understand the mechanisms underlying transformation of esophageal and gastrointestinal epithelium and its relationship with developmental processes, we studied and compared the expression of the intestine–specific homeodomain protein CDX2 and protein p63 in digestive system of human embryos and fetuses. CDX2 staining was only seen in the nuclei of small and large intestinal epithelium. To obtain more insight into the role of p63 in the morphogenesis of these epithelia, we examined the p63 expression that was detected in the esophagus in early embryonic period and late fetal one. We hypothesized, that p63 may exert essential roles in regulating the switch between different types of epithelia. Based on our results, we suggest that the lack of p63 expression in the esophageal cells results in the transdifferentiation of one epithelial type into another one.