Modern multiphase diagnostic imaging allows diagnosis of hepatocellular carcinoma with high specificity in a large proportion of cases. Additional aspects of tumor biology also can be evaluated noninvasively through observation of tumor behavior (growth rate, satellites, vascular invasion) and other indicators of tumor biology (avid uptake of fluorodeoxyglucose, high circulating levels of tumor markers such as alphafetoprotein). Routinely requiring biopsy confirmation for diagnosis of HCC exposes many patients to unnecessary risk, may delay diagnosis, and in some cases leads to withholding of potentially beneficial treatment. Biopsy for assessment of tumor molecular markers is promising but remains investigational. When diagnosis of HCC is clinically evident by imaging criteria, tumor biopsy should not be required prior to initiating treatment.