Hepatocellular carcinoma (HCC) is the most common primary malignant neoplasm of the liver. Approximately 90% of these tumors arise in the background of cirrhosis secondary to an underlying liver disease, such as infection with hepatitis B or C virus, alcoholic liver disease, nonalcoholic steatohepatitis, or autoimmune hepatitis. In most cases, larger tumors can be reliably diagnosed on imaging studies when they show arterial enhancement and portal venous washout on dynamic contrast-enhanced CT or MRI studies. This characteristic imaging pattern is due to the increased arterial supply of the tumor compared to the surrounding liver. Smaller tumors may be more difficult to characterize by imaging studies. Tumors smaller than 2 cm may be classified as a very early or “vaguely nodular” HCC which have a poorly defined border or progressed HCC which have a more distinct border [1, 2]. These very early HCCs do not generally have the complete alterations in the blood supply characteristic of progressed tumors and thus lack the features required for diagnosis on imaging. According to the American Association for the Study of Liver Diseases practice guidelines, tumors arising in a cirrhotic liver that are larger than 1 cm and show the characteristic findings of arterial enhancement and portal venous washout on dynamic imaging can be diagnosed as HCC without the need for a biopsy, while liver biopsy may be required when the imaging features are not characteristic [3]. As the understanding of the molecular pathogenesis of HCC advances, tissue samples may soon be required even in radiologically diagnosed HCC for the purposes of assessing prognosis and tailoring therapy.