Prolonged reflux esophagitis leads to replacement of the esophageal squamous epithelium by columnar epithelium in some patients. This columnar epithelium resembles gastric or intestinal mucosa and has been implicated as a precursor of esophageal adenocarcinoma. A review of 14 cases of primary esophageal adenocarcinoma disclosed that 12 (86%) arose in a columnar epithelium-lined (Barrett's) esophagus. Ten of the 12 patients had a hiatal hernia or symptoms of reflux esophagitis or both. In ten patients the columnar epithelium adjacent to and remote from the invasive adenocarcinoma showed a spectrum of abnormalities ranging from mild dysplasia to carcinoma in situ. These data support the concept that esophageal adenocarcinoma is one complication of a columnar epithelium-lined esophagus, and suggest that the invasive carcinoma evolves through a sequence of epithelial dysplasia and carcinoma in situ in most cases. Esophageal biopsy and cytology can detect this dysplasia, and should provide an effective means for monitoring patients with Barrett's esophagus for impending malignancy.