Hepatocellular carcinoma (HCC) is a malignant neoplasm composed of cells with a hepatocellular differentiation. Most HCCs exhibit a trabecular and/or acinar histologic pattern (ordinary or classical HCC), but there also exist numerous variants with a different morphology and a fibrolamellar variant treated in a separate chapter. HCC is a frequent malignancy and is estimated to be the fifth most common malignancy in males worldwide. Most of the tumors arise in patients with liver cirrhosis caused by various etiologies, hepatitis virus infections, and toxic agents playing a central role. HCC displays specific macroscopic growth patterns. Eggel divided the neoplasms in nodular, massive, and diffuse types, nodular HCC being the most common. This classification has subsequently been extended and refined. HCC frequently invades large and small hepatic vessels and bile ducts, causing distinct clinical disorders. Histologically, hepatocyte-like cells arranged in large plates with an abnormal reticulin pattern and loss of Kupffer cells are the hallmarks of trabecular HCC, whereas pseudoglandular structures are found in other tumors. The grading of HCC has been standardized and is an important prognosticator. Morphological classifications of HCC are currently extended by the use of molecular signatures of these neoplasms. Table 1 Age-adjusted incidence of HCC per 100,000 inhabitants (Llovet et al. 2003; modified) Area Age-adjusted incidence (males/ females) Worldwide 14.9/5.5