Esophageal cancer is a common malignancy with a striking variation in geographical distribution; a reflection of exposure to specific environmental factors, which are still poorly defined. We discuss the recent progress made in the investigation of the molecular biology of esophageal cancer, addressing the topics of genetic alterations, methylation, overexpression of molecules thought to cause malignant transformation, carcinogenesis, invasion, and metastasis. We review six aspects of the research literature on esophageal cancer: epidemiology and etiology, epidermal growth factor receptor and related growth factor receptors, cell cycle regulatory proteins, transforming growth factor-beta/Smad proteins, mismatch repair genes, and other genes. This article provides a conceptual basis for evaluating studies on the molecular mechanism of esophageal carcinogenesis and for devising therapeutic and preventive strategies based on molecular biology. We hope that in the near future, the clinical outcome of patients with esophageal carcinoma will be improved by a better understanding of the basic mechanisms of carcinogenesis.