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Hepatocellular carcinoma (HCC), a common malignancy in the United States with poor prognosis, must be differentiated from hemangioma, focal fat, metastases, and regenerating nodules. Serum α-fetoprotein (AFP) levels are not a sensitive method for detection of HCC. High resolution ultrasound has been highly effective in detecting HCC in Japan and Taiwan. Doppler ultrasound can be used to increase the specificity. We review the roles of angiography, computed tomography (CT), and magnetic resonance, to conclude that the Japanese experience has demonstrated the efficacy of screening for HCC in the population at risk using serum AFP and ultrasound with the addition of dynamic CT and angiography where indicated. The continuing poor prognosis of patients with HCC in the United States suggests a failure to apply these methods for the early detection of HCC.