Several cases of Acanthamoeba encephalitis (ie, granulomatous amebic encephalitis) have been reported in patients with acquired immunodeficiency syndrome from the United States. To our knowledge, none so far has been reported from Europe, and this is the first case of amebic meningoencephalitis due to Acanthamoeba in a patient with acquired immunodeficiency syndrome from Italy. The patient was a 24-year-old, human immunodeficiency virus-positive heterosexual man with a 6-year history of intravenous drug use. He was admitted to the hospital because of severe headache, confusion, nuchal rigidity, jaundice, and ascites. He died 5 days later. At autopsy, the brain showed extensive hemorrhagic necrosis with numerous trophic and cyst forms of Acanthamoeba. The amebas were identified as Acanthamoeba divionensis by the indirect immunofluorescence test.