Patients with compensated cirrhosis (and low Model for End-Stage Liver Disease score) should not undergo transplantation unless they have small hepatocellular carcinoma (HCC). Therefore, presence of HCC should be definitely ascertained before deciding on transplantation in this group of patients. Current imaging techniques allow detection of small liver nodules (<1 cm). Not all liver nodules between 1 and 2 cm are HCC. In addition, benign regenerative nodules have a relatively low potential for degeneration. It is generally agreed that in patients with evidence of cirrhosis, a definitive diagnosis of HCC can be made without tissue analysis in case of nodules >2 cm with a characteristic pattern on either computed tomography (CT) or magnetic resonance imaging (MRI) (hypervascularity in the arterial phase and washout in the early or delayed venous phase). Two concordant imaging techniques (triphasic CT and MRI) are needed to ascertain HCC in case of nodules between 1 and 2 cm. Biopsy is needed for making a diagnosis of HCC in patients with cirrhosis with nodules that do not fulfill the above criteria. Whatever the characteristics of the nodules, biopsy should also be performed in patients without documented cirrhosis. In case of HCC, percutaneous biopsy carries a risk of needle tract seeding of 1-2%. Percutaneous biopsy carries a potential risk of hematogenous dissemination that has not been clearly assessed. There is no clear evidence that the risk of posttransplantation recurrence is higher in patients who undergo biopsy before transplantation. Therefore, in case of HCC, previous biopsy should not be considered a contraindication for transplantation. Even though the specificity of biopsy is close to 100%, its negative predictive value is low. Negative biopsy findings do not exclude the presence of HCC. Patients with negative biopsy findings should either undergo a second biopsy or an enhanced surveillance protocol.