African histoplasmosis is the relatively unknown infection by Histoplasma capsulatum var. duboisii. It is endemic to Central and West Africa, generally involving the skin with potential for systemic dissemination, and has been described mainly in immunocompetent hosts. We present the case of a 30-year-old Bissau-Guinean man with HIV-2 infection known for 16 years, irregularly treated, admitted with two weeks of fever, diarrhoea and cutaneous lesions. Examination revealed multiple subcutaneous nodes, Molluscum contagiosum-like lesions, generalized lymphadenopathy and painful palpation of the left iliac fossa. Laboratory tests showed severe nonhaemolytic anaemia and CD4+ count of 9/mm3, with normal creatinine and hepatic enzymes. Chest roentgenogram was unremarkable and a research for Mycobacterium tuberculosis by GeneXpert® was negative. Nonetheless, given the lack of further diagnostic tools, a presumptive diagnosis of disseminated tuberculosis was made, and the patient was started on tuberculostatic and antiretroviral drugs. Despite initial improvement, a national shortage of antiretrovirals precluded further treatment, with worsening of the clinical picture, namely an increase in the number and dimensions of the skin lesions. An excisional biopsy of a subcutaneous nodule revealed Histoplasma capsulatum var. duboisii. Unfortunately, due to the unavailability of antifungals, the patient died one week later. To our best knowledge, this is the first confirmed case of an HIV infected patient with African histoplasmosis in Guinea-Bissau.