Fine-needle aspiration biopsy was performed in 240 patients with suspected pancreatic or biliary tumors between 1978 and 1984. Between 1978 and 1982, using only sonographic guidance, the sensitivity of the technique was 66.7% for pancreatic and 40% for biliary tumors compared with 79.4% for carcinomas in other locations. The main reasons for failure to obtain positive cytology were small tumor size and sampling errors. From 1983 onward, combined sonographic and fluoroscopic biopsy guidance with opacification of the bile duct or pancreatic duct was routinely used together with heavier sedation to allow more careful needle placement. The sensitivity of the technique improved from 1983 to 1984 and was 77.5% for pancreatic tumors and 60% for biliary tumors. Failure of the cytologic technique to identify well-differentiated tumors and lymphomas has become a major source of tumor misdiagnosis.