In Barrett's esophagus, stratified squamous mucosa of the lower third of the esophagus is replaced by columnar mucosa, as a complication of chronic gastroesophageal reflux. The presence of Barrett's esophagus appears to be a major factor in the progression to adenocarcinoma of the lower third of the esophagus. Therefore it is crucial to identify the subset of patients at risk for the development of adenocarcinoma. Dysplasia is an important histologic feature to evaluate because it identifies those patients who require follow-up. The diagnosis of biopsies with lesser degrees of abnormalities, however, makes microscopic evaluation less helpful in identifying patients who need more frequent endoscopic biopsy surveillance. DNA ploidy and the use of monoclonal antibodies, such as suppressor gene product p53, oncogene cerbB-2, and Ki-67, have added dramatically to our understanding of the biology of Barrett's metaplasia and have given us objective indicators to predict the presence of an increased risk of developing cancer.