Disseminated histoplasmosis in South America is associated with AIDS in 70-90 % of cases. It is visceral and cutaneous, compromising the oral, pharynx, and laryngeal mucous membranes. The involvement of the nasal mucosa is unusual. Two patients with perforation of the nasal septum as the only sign of their disease were clinically and histopathologically diagnosed as leishmaniasis. The revision of the biopsies and the culture of nasal discharge secretions showed that the pathogens seen were not amastigotes but Histoplasma capsulatum. Other mycotic lesions were not detected, nor there was history of cutaneous leishmaniasis. The leishmanin skin test, available only for the male patient, was negative. The PCR and immunofluorescence antibody titers for Leishmania were negative in both patients. They were HIV positive; in the male, his CD4+ T cell count was 60/mm(3) and in the female 133/mm(3). The nasal ulcer was the only manifestation of histoplasmosis and the first of AIDS in both patients. The male patient recovered with amphotericin B and itraconazole treatment. The female has improved with itraconazole. Both patients received antiretroviral treatment. Nasal mucous membrane ulcers should include histoplasmosis among the differential diagnosis. In conclusion, two patients had perforation of their nasal septum as the only manifestation of histoplasmosis, a diagnosis confirmed by nasal mucosa biopsy and by culture of H. capsulatum, findings which demonstrated that both patients had AIDS.