Acute liver failure (ALF) is a rare condition in which liver function deteriorates suddenly, leading to encelopathy and coagulopathy in patients previously unaffected with hepatic cirrhosis. The case is presented of a 60-year-old woman admitted to our Department with complaints of general malaise, excessive sweating and body temperature elevation. Her history was relevant in terms of T-cell lymphoma in remission, hypertension and paroxysmal atrial fibrillation. The patient only reported using methylprednisolone in 4–8 mg daily dosage. Liver function tests were abnormal, with considerably elevated ALT, AST and GGTP concentrations. Diagnostic imaging revealed non-dilated biliary ducts, hepatomegaly and a single enlarged lymph node between the inferior vena cava and hepatic portal vein. A needle biopsy of the liver was non-diagnostic due to protein masses blurring the specimen. Autoimmune markers and investigation for Wilson’s disease both presented no alterations. The patient presented hyperthyroidism with no signs of thyrotoxicosis, significant leukocytosis with granulocytosis and thrombocytopenia. Her state deteriorated rapidly despite aggressive pharmacological treatment. The patient died before a needle core biopsy could be performed; no post-mortem examination was carried out at the request of the family. ALF should be suspected in every patient who exhibits highly elevated hepatic enzymes and whose condition is deteriorating rapidly. In our investigation, we should primarily focus on histopathological examination and qualifying the patient for the liver transplantation.