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Herein we report the case of hepatic amoebic abscesses in an HIV-positive Italian seaman with a history of promiscuous heterosexual intercourse. In October 2004, the patient was hospitalized because of fever and recurring abdominal pain. Abdominal ultrasonography revealed six hepatic hypoechoid oval lesions with hyperechoid margins. Stool samples were negative for parasites and bacteria, and serology for Entamoeba histolytica was also negative. Therapy with meropenem plus levofloxacin was initiated. After a partial resolution of clinical symptoms and reduction of three hepatic lesions, the patient was again hospitalized in December 2004, because of recurring intense pain at the right hypochondrium and fever. At this time, one hepatic lesion at the sixth segment was enlarged, two lesions were unchanged, and the remaining three smaller abscesses were resolved. Serum antibodies for E. histolytica and amoebic antigens on the largest abscess drainage were positive; moreover, E. histolytica was also identified on drainage fluid with polymerase chain reaction (PCR). Therapy with metronidazole followed by paromomycin improved both symptoms and radiographic images. This case report suggests that in HIV-infected patients, invasive amoebiasis should be considered and atypical aspects, such as multiple hepatic lesions, delayed positivity of serology for E. histolytica, and possible bacterial superinfection should be evaluated.