Hepatocellular carcinoma (HCC) is the most common primary malignancy arising within the liver and most often affects individuals with chronic hepatitis and/or liver cirrhosis. Patients often present at an advanced stage of disease or with poor liver function, thus limiting treatment options and resulting in a poor prognosis of the disease. Therefore, an early tissue-based diagnosis of HCC is necessary to direct further work-up and treatment. We present the case of a 70-year-old man with alcoholic cirrhosis at stage Child C, in whom a tumor nodule was found incidentally within the left lobe of the liver. Percutaneous biopsy was deemed too dangerous because a deteriorated liver function with coagulopathy was present, and a significant amount of ascites surrounded the small cirrhotic liver. To obtain a conclusive diagnosis, we performed transgastric fine-needle biopsy of the tumor under direct endosonographic guidance (EUS-FNA) without complications. Cytologic examination confirmed the presence of a well differentiated HCC. Based on this finding, super-selective CT-guided angiography and chemoembolization were subsequently performed without complications and the patient remained free of tumor relapse for the 8 months of surveillance. We conclude that EUS-guided fine-needle biopsy and cytologic examination represent a reliable alternative for tissue sampling in HCC, particularly in selected high-risk patients such as those with poor liver function and coagulation disorders; this should be assessed in prospective clinical trials.