The following is a report on one case of successful biopsy of a hepatic focal lesion incidentally found in an emergency computed tomography scan performed in a patient with acute liver failure clinical presentation. The presence of peri-hepatic ascites and severe coagulopathy contraindicated the percutaneous biopsy. The transjugular approach was used to perform a random liver biopsy to assess the amount of hepatic necrosis and to perform the focal lesion biopsy orienting the needle with sonography guidance. The specimen acquired was satisfactory to exclude the presence of malignant cells in the lesion; the diagnosis of atypical focal nodular hyperplasia was performed. The patient underwent successful liver transplantation the day after.