In a 28-year-old man with a long history of esophageal reflux, two polypoid lesions in a columnar-lined (Barrett) esophagus proved to be adenopapillary cancer. Despite extensive preoperative endoscopic evaluation, no other malignant foci were found until after complete postoperative dissection of the esophageal specimen, when two more small flat lesions were diagnosed as adenocarcinoma. Dysplastic changes of specialized columnar epithelium and junctional epithelium were mild, except around the tumors. In the preoperative assessment of patients with a columnar-lined esophagus, physicians should be aware of the possibility of multifocal development of tumors either exophytic or superficial spreading, and multiple biopsies should be taken from normal-looking areas.