Esophageal cancer displays unique epidemiologic features that distinguish it from all other malignancies. It shows marked geographic variation both internationally, with exceptionally high rates (some of the world's highest for any cancer) in limited areas of Asia, and nationally, with clustering of increased rates within the United States as well. However, the patterns are changing with rates of squamous cell carcinomas decreasing and adenocarcinomas increasing rapidly in several western countries. The causes of the clusters of squamous cell carcinomas in parts of Asia and Africa are not well known, but within the United States and other western countries, tobacco and alcohol consumption are the major determinants. Nutritional factors also may play a major role, with diets high in fresh fruits and vegetables consistently associated with reduced risks. The causes of the rapidly increasing rates of adenocarcinomas of the esophagus, and reasons or its occurrence primarily among white men, are enigmatic. Additional research on the etiology of this emerging cell type is warranted, and may provide information crucial to the development of readily implementable preventive strategies.