Neoplastic development in the esophagus is characterized by abnormal activity in the basal cell proliferative compartment. Malignancy starts with mild dysplasia. Barrett's esophagus is associated with columnar epithelial dysplasia and presents increased risk for adenocarcinoma. Esophagitis, especially with chronicity, may constitute a predisposing characteristic in high incidence areas. This paper briefly describes the main features of precancerous lesions in the esophagus. It then focuses on a discussion of the biological markers of malignancy in the oral cavity and esophagus that are currently under study. Such biomarkers include promising differentiation markers such as keratins, involucrin, particulate transglutaminase, as well as growth factors, and most studied but nonspecific onco-developmental markers, e.g., carcinoembryonic antigen, alpha 1-fetaprotein, hormone/enzyme markers, e.g., human chorionic gonadotropin and placental lactogen, and a number of other miscellaneous markers.