The eukaryotic translation initiation factor 4E (eIF4E) has been shown to play a key role in cell growth, and several studies have documented an increased expression of eIF4E in a number of solid tumors, including breast, bladder, cervical, and head and neck cancers. This study was done to evaluate the potential role of eIF4E in the polyp-cancer sequence in the colorectum. Eighty-seven cases with lesions in the colorectum with a variety of histopathological diagnoses were randomly selected from the archives of the Pathology Department at Louisiana State University Health Sciences Center-Shreveport. Appropriate sections were selected for immunostaining with eIF4E. The medical records of the patients were reviewed, and demographic information was collected. All statistical analyses were performed using SAS software. A statistically significant relationship was found between the level of eIF4E expression and histological type of lesion: the lowest level of eIF4E expression was found in normal colon tissue, whereas the highest level of eIF4E expression was found in colorectal adenocarcinomas. Carcinomatous lesions were found to have a 43 times higher chance of having a high level of eIF4E expression compared with normal tissue (95% confidence interval, 8.0-213.6, P < 0.0001). In a multivariate analysis, histological type was the only variable that showed a significant relationship with eIF4E expression; no effect was found due to age, gender, race, history of polyps, and family history. The results from this study are consistent with other data from the literature and support the suggestion that eIF4E is strongly involved in colon tumorigenesis. eIF4E might be a useful intermediate biomarker for use in chemoprevention intervention studies in patients with colorectal polyps.