The risk of hepatocellular carcinoma superimposed in the evolution of autoimmune hepatitis or primary biliary cirrhosis is low, even in patients with long-standing cirrhosis. We report a case of hepatocellular carcinoma occurring in a 46 year old woman with liver cirrhosis following overlap syndrome between autoimmune hepatitis and primary biliary cirrhosis, routinely followed while on the waiting list for liver transplantation. The patient had combined biochemical (elevated aminotransferases, alkaline phosphatase and gamma-glutamyl-transpeptidase in the range of 2-3 times above the upper limit of the normal) and serological (anti-smooth muscle antibody > 1/80 and anti-mitochondrial antibody anti-M2 > 1/40) criteria of autoimmune hepatitis and primary biliary cirrhosis. Hepatocellular carcinoma was diagnosed in the setting of chronic liver disease by the combination of two concordant imaging technics (Doppler ultrasound and magnetic resonance imaging) showing a hepatic nodule with arterial hypervascularization and elevated serum levels of alpha-fetoprotein up to 950 ng/ml. Liver transplantation is the best treatment both for the solitary nodule less than 5 cm and underlying autoimmune cirrhosis. Using the new Model for End-Stage Liver Disease allocation system our patient was placed in a prior position for liver transplantation (MELD 29). Unfortunately, a sudden fulminant liver failure complicated with intravascular disseminated coagulopathy was fatal for our patient while awaiting liver transplantation.