Epithelial glycoprotein EGP-2 and carcinoembryonic antigen (CEA) are transmembrane glycoproteins and cell surface markers. Eighty-four colorectal tumors including 23 adenomas (2 mild, 13 moderate, and 8 severe atypia) and 61 adenocarcinomas (33 well- and 28 moderately differentiated) as well as adjacent normal colonic mucosa (51 cases) were studied for the immunolocalization of EGP-2 as detected by the monoclonal antibody VU-1D9, and compared with CEA expression. In the normal colonic mucosa, basolateral VU-1D9 expression in the surface epithelial cells was constantly seen in all 51 cases, while weak apical CEA staining in the surface epithelium was seen in 25% (13/51) of the cases. In 91% (21/23) of the adenomas, regardless of the grade of atypia, VU-1D9 labeled the basolateral membrane of a few surface lining cells leaving atypically proliferating glands negative, while CEA expressed strong apical staining in the surface epithelial cells as well as atypically proliferating glands. The well-differentiated adenocarcinomas showed homogeneous basolateral staining for VU-1D9 and strong apical staining for CEA; the moderately differentiated adenocarcinomas showed membranous as well as cytoplasmic VU-1D9 staining and luminal as well as cytoplasmic CEA staining. The VU-1D9 and CEA localizations and the stage of expression in relation to tumor progression were completely different. Strong CEA expression was seen in the adenomatous stage, while the homogeneous VU-1D9 expression required tumor progression to the carcinomatous stage. VU-1D9 especially when applied in combination with CEA, will be a useful marker for colorectal lesions, and its reactivity patterns in carcinoma can predict the prognosis.