Aberrant crypt foci (ACFs) may be the earliest recognizable histologic precursor lesion for colon cancer. ACF may develop from a complex of events, including the development of cryptal hyperproliferation, defects in the rate of apoptosis, and abnormalities in cellular adhesion. In this study, we hypothesized that human ACF would exhibit discrete differences in cell adhesion proteins compared with normal mucosa of biologic markers associated with colon cancer. ACFs were isolated from resected colon mucosa from 45 patients undergoing surgery for colon cancer. We evaluated the protein expression of 3 biologic markers that may be related to the progression of aberrant crypt foci to tumors: carcinoembryonic antigen, E-cadherin, and sialyl Tn antigen. In general, ACFs located near cancers in the right colon were more often hyperplastic than dysplastic; this was more noticeable in the left colon. Carcinoembryonic antigen expression was found to be more intense in apical portions of ACF crypts, with sialyl Tn antigen moderately increased, whereas E-cadherin diffusely stained throughout crypts within ACFs. There are significant biologic changes in potential tumor markers that accompany the early transformation of the normal glandular epithelium, some of which are expressed very early in the colon at the stage of appearance of ACF.