The clinical features and usefulness of various methods for diagnosis of small hepatocellular carcinoma, no greater than 5 cm in diameter, were studied in 51 patients. The diagnosis was verified in 28 patients by hepatic resection and in 4 patients at autopsy. The tumor was less than 3 cm in diameter in 23 patients. In 37 patients (72.5%), the tumor was first discovered by real-time linear scan ultrasonography, generally during a routine periodic follow-up examination of patients with chronic liver disease, mostly cirrhosis. Clinically, 62.7% of the patients were asymptomatic, and symptoms in the remainder were not suggestive of carcinoma. Most patients showed only mildly abnormal liver function tests that did not suggest the diagnosis. Serum alpha-fetoprotein level was normal in 25.5%, and it was elevated above 200 ng/ml in only 33.3%. Among the various imaging modalities, ultrasonography had the highest detection rate (92.2%) for these small hepatocellular carcinomas compared with computed tomography (73.2%), scintigraphy (50.0%), and angiography (86.0%). False-positive lesions, however, were also found frequently by ultrasonography, requiring ultrasonography-guided biopsy for differential diagnosis in some of the patients. Routine examination at regular intervals of patients with chronic liver disease using a combination of real-time ultrasonography and alpha-fetoprotein measurement is currently the most effective approach to detecting small hepatocellular carcinoma.