A prospective trial was performed in which biopsy and cytology specimens were obtained on 202 consecutive patients including 47 with esophageal or gastric carcinomas. The first biopsy specimen yielded a correct diagnosis in the majority of instances: 70% of gastric carcinomas and 93% of esophageal carcinomas. Three additional biopsy specimens increased the yield to greater than 95%, a total of seven biopsy specimens yielded greater than 98%. Seven biopsy and cytology specimens yielded the correct diagnosis in all patients. Seventeen percent of all lesions subsequently proven to be malignant were thought to be benign, endoscopically. This reinforces the belief that all lesions seen at endoscopy should have biopsies performed and at least seven specimens should be obtained.