Because of the high rate of diagnostic error with routine Ba X-ray studies in detection of upper gastroesophageal lesions, a prospective investigation was undertaken to evaluate endoscopy together with brushing cytology and biopsy. Ninety-nine patients with recurrent upper gastrointestinal [GI] symptoms were examined during a 2 yr period. Thirty-seven patients had cancer and 62 had benign ulcers as diagnosed by cytology and histopathology. All patients with diagnosis of carcinoma were correctly diagnosed by a combination of these studies as proven by subsequent surgical exploration of all 37 patients. In the benign group, 23 patients were confirmed by exploratory laparotomy and 16 patients by follow-up for at least 2 yr with upper GI series and/or endoscopy. The highest degree of accuracy in the diagnosis of cancer was achieved by cytology alone (92% of cases) and lowest by Ba study of upper GI tract (84% of cases). Although the accuracy of endoscopy in detecting cancer of the upper GI tract was 86%, 15% of benign ulcers were falsely called neoplastic by this technique. Endoscopy with brushing cytology and biopsy is an effective diagnostic tool in distinguishing benign lesions from malignant neoplasms and can be performed with little risk to the patient.