The diagnosis of hepatocellular carcinoma (HCC) includes detection of the index lesion, staging of the lesion within the liver, and assessment for extrahepatic metastasis. HCC is a highly vascular neoplasm usually arising in a cirrhotic liver. Based on this concept, consensus criteria have been developed for the radiographic diagnosis of HCC. These include: (1) identification of a mass >2 cm in diameter in a cirrhotic liver in 2 imaging modalities, and (2) contrast enhancement on computed tomography, magnetic resonance, or angiography. A mass lesion within a cirrhotic liver in the presence of a serum alpha-fetoprotein level >400 ng/mL also is diagnostic. For lesions <2 cm in diameter, histological confirmation is required. Serum markers for the diagnosis of early HCC (<2 cm in diameter) have not been established. Staging HCC for metastases is insensitive and is based on conventional criteria (eg, pulmonary nodules, skeletal metastases, and lymphadenopathy). Additional diagnostic techniques based on cytological advances, genomics, and proteomics are needed for the diagnosis and staging of this highly malignant neoplasm.