Adenocarcinoma begins in the cells of mucus-secreting glands in the esophagus. Adenocarcinoma occurs most often in the lower portion of the esophagus. Adenocarcinoma is the most common form of esophageal cancer in the United States, and it affects primarily white men. Esophageal cancer usually originates in the inner layers of the lining of the esophagus and grows outward. In time, the tumor can obstruct the passage of food and liquid, making swallowing painful and difficult. Since most patients are not diagnosed until the late stages of the disease, esophageal cancer is associated with poor quality of life and low survival rates. Squamous cell carcinoma is the most common type of esophageal cancer, accounting for 95% of all esophageal cancers worldwide. The esophagus is normally lined with thin, flat squamous cells that resemble tiny roof shingles. Squamous cell carcinoma can develop at any point along the esophagus but is most common in the middle portion.

Adenocarcinoma has surpassed squamous cell carcinoma as the most common type of esophageal cancer in the United States. Adenocarcinoma originates in glandular tissue not normally present in the lining of the esophagus. Before adenocarcinoma can develop, glandular cells must replace a section of squamous cells. This occurs in Barrett's esophagus, a pre-cancerous condition in which chronic acid reflux from the stomach stimulates a transformation in cell type in the lower portion of the esophagus.A very small fraction of esophageal cancers are melanomas, sarcomas, or lymphomas.There is great variability in the incidence of esophageal cancer with regard to geography, ethnicity, and gender. The overall incidence is increasing. About 13,000 new cases of esophageal cancer are diagnosed in the United States each year. During the same 12-month period, 12,000 people die of this disease. It strikes between five and ten North Americans per 100,000. In some areas of China the cancer is endemic.