The authors report two cases of disseminated histoplasmosis occurring in HIV-infected patients living in French Guiana. The first case was an acute disseminated histoplasmosis with a rapid fatal evolution. The second case was diagnosed on a mucosal localisation, and improved under itraconazole therapy. These two cases show the diversity of the clinical course of this opportunistic infection. The authors focus on the difficulty of the diagnosis and the need for direct microscopic examination to identify histoplasma and to enable a swift therapeutic intervention.