The frequency, therapeutic management, and prognosis of multifocal carcinomas within the esophagus, and of synchronous or metachronous malignancies in other organs were prospectively studied in a series of 798 consecutive patients with primary esophageal and cardial tumors. One hundred and seven patients (13.4%) had more than one primary: 59 (7.4%) were synchronous and 48 (6%) metachronous. Eighty-six patients (10.8%) had multiple synchronous or metachronous malignancies of the upper digestive tract. Sixty of these patients had ENT tumors. A high index of suspicion, systematic panendoscopy with vital staining, and multiple biopsies were highly effective in the early detection of multiple tumors. Resection was possible in 47 selected cases. Aggressive surgical management seems to be justified by some long-term survivors, relief from symptoms, and improvement of general status obtained in most cases.