The late occurrence of a large and often long-lasting effusion in the pleural and peritoneal cavities after liver transplantation is an uncommon and poorly understood complication. Even rarer (<1%) is the incidence of Mycobacterium tuberculosis (MT) in Western world series. Herein we have described a case of massive pleural effusion and ascites due to MT occurring 22 months after liver transplantation for hepatitis C virus (HCV) cirrhosis. The infection was successfully treated with no hepatotoxicity or rejection, so that it was possible to start antiviral treatment with peginterferon and ribavirin for recurrent HCV without reactivation of MT infection.