In a prospective study of 54 consecutive patients where carcinoma of the pancreas was suspected, a simple protocol was employed. Each patient had duodenoscopy and pancreatic juice cytology. Those patients with jaundice had cholangiography by percutaneous or endoscopic retrograde technique. Patients who were not jaundiced had endoscopic retrograde cholangiopancreatography. Malignancy, confimed by histology, was diagnosed in 25 patients. Patients diagnosed as having benign disease were followed for 2 yr, and in none has the diagnosis changed to malignancy. Of those with carcinoma, 21 were correctly diagnosed on the basis of cholangiograms or pancreatograms, but there were 2 false-positive diagnoses of malignancy. Cytology identified 15 of the 25 with carcinoma; there were no false-positive diagnoses. Pancreatic cytology is highly specific for the diagnosis of carcinoma and should be used early. In patients with negative cytology, an acceptable level of accuracy can be achieved by a combinatin of endoscopy and radiology.