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Alpha-fetoprotein (AFP), the major protein component of fetal serum, is synthesized by the visceral endoderm of the yolk sack during early fetal life and subsequently by the fetal liver. Immediately after birth levels fall rapidly to become virtually undetectable and rise again only when certain pathologic conditions develop. It has been known for almost 40 years that re expression of AFP consistently occurs in patients with hepatocellular carcinoma (HCC), and on this basis AFP became one of the first clinically useful tumor markers. For those involved in the management of patients with HCC, AFP plays a central role in day-to-day clinical practice.