Over the past two decades, the incidence of adenocarcinoma of the esophagus and gastric cardia has increased at a rate exceeding that of any other cancer. Barrett's esophagus is the only known risk factor for these malignancies. Recently, emphasis has been placed on the significance of specialized intestinal metaplasia (SIM) on esophageal biopsies. Our aim was to compare the prevalence of SIM at different esophageal locations in patients who are at higher risk of developing esophageal adenocarcinoma (Caucasians) and patients with lower risk of developing esophageal adenocarcinoma (African-Americans). Eighty-seven unselected patients (42 Caucasians and 45 African-Americans) underwent routine upper endoscopy with biopsies from the proximal margin of columnar mucosa. We classified patients into those with a columnar-lined esophagus with SIM (CLE with SIM); CLE without SIM; or SIM with a normal-appearing gastroesophageal junction (SIM-GEJ). The prevalence of CLE with SIM, CLE without SIM, and SIM-GEJ was 28%, 10%, and 10% in Caucasians compared to 0%, 18% and 11% in African-Americans (P = 0.0001, 0.26, and 0.81, respectively). We found CLE with SIM only in patients with reflux symptoms at least twice a week. It is concluded that CLE with SIM is seen most commonly in patients thought to be at risk for esophageal adenocarcinoma (Caucasians with reflux symptoms). It is rarely seen in other groups with lower risk for this malignancy (African-Americans, nonrefluxers). Conversely, SIM-GEJ and CLE without SIM are common in all groups and are of questionable significance.