Barret's esophagus develops when metaplastic columnar cells replace esophageal squamous cells that have been damaged by the reflux of noxious gastric material. Epidemiologic evidence suggests that Barret's epithelium usually develops all at once, and does not progress substantially in extent over time, despite ongoing gastroesophageal reflux disease. Barret's esophagus is the single most important risk factor for esophageal adenocarcinoma. Carcinogenesis in Barret's epithelium appears to involve the activation of protooncogenes such as c-erbB2, and the dysfunction of tumor suppressor genes likep53. Activation of growth factor receptors may also contribute to carcinogenesis, and Barret's epithelium has been found to express epidermal growth factor receptor and its ligands. Barret's specialized columnar epithelium, the type most often associated with malignancy, appears to have an expanded proliferative compartment with a high proportion of cells in cycle.