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We report a case of disseminated infection with Mycobacterium genavense in a 58 year old HIV positive woman presenting with fever, diarrhea, abdominal pain and weight loss. She had a striking hepatosplenomegaly, abdominal lymphadenopathy, anaemia and thrombopenia. Direct smears and cultures of blood, stool, sputum, urine and bone marrow were negative for common and opportunistic microorganisms. Splenectomy revealed numerous acid fast bacill. Lumbar puncture also showed acid fast bacilli at direct examination. Specific PCR and 16s rRNA gene sequencing identified M. genavense. The outcome was fatal despite antimycobacterial therapy. M. genavense must be included in the differential diagnosis of fever, weight loss, lymphadenopathy and splenomegaly in immunocompromised patients. Prompt diagnosis is based on molecular biology methods. Empirical therapy, using at least three antimycobacterial agents, including clarithromycin should be introduced in case of high clinical suspicion.