Hepatocellular carcinoma is a rapidly fatal tumor that usually becomes symptomatic only at a stage beyond the reach of currently available treatments. The only hope for a cure lies in early diagnosis. It follows that an effective screening strategy should be used in high-risk populations, including patients with cirrhosis due to any cause, patients with chronic hepatitis B or C, and asymptomatic carriers of the B virus genome (and probably the C virus genome). Screening currently relies on physical examination and on two investigations, ultrasound scanning and the alpha-fetoprotein (AFP) assay, whose sensitivity and specificity vary with tumor size. The optimal interval between evaluations seems to be four to six months, although large prospective studies confirming this are not yet available. Because the AFP assay lacks sensitivity and specificity in patients with small tumors, other serum markers are being evaluated. In parallel, hepatitis B immunization and alpha interferon therapy of chronic hepatitis C are expected to decrease the incidence of hepatocellular carcinoma.