Two hundred patients underwent ultrasound-guided percutaneous fine-needle aspiration biopsies of hepatic and pancreatic space-occupying lesions. In addition to the cytologic smear preparations (100%), tissue fragments and cores suitable for histological evaluation were obtained from aspirated samples in 84% of specimens from hepatic targets (n = 130) and in 61% of specimens from pancreatic lesions (n = 70). The prevalence of malignant disease was 78.5% in the liver study group and 74.3% in the patients undergoing pancreatic biopsies. The overall accuracy rate of cytohistologic readings for malignancy was 94.6% in liver biopsies and 92.9% in pancreatic biopsies with a high predictive value of positive results of 98% and 100%, respectively, and a less satisfying predictive value of negative results of 83.9% and 77.3%, respectively. Two false-positive diagnoses were encountered in the evaluation of cytologic smear preparations of hepatic aspirations. No serious complications occurred with the biopsy procedure. Ultrasound-guided fine-needle biopsy is recommended as a safe and reliable method for cytohistological confirmation of suspected hepatic and pancreatic malignancy.