An analysis of the molecular events underlying the development of esophageal cancer may yield new strategies for diagnosis, prevention, and therapy. Oncogenes and tumor suppressor genes have been implicated in the development of esophageal cancer. Tumor suppressor gene mutations are present in Barrett's epithelium, the premalignant lesion for adenocarcinoma. Early genetic changes may predict the development of invasive cancer. Recent data suggest that reversal of single gene abnormalities can reduce the tumorigenic potential of cancer cells.