Among bone lesions of African histoplasmosis, those affecting the jaw are relatively rare and concern, with other facial involvements, particularly infants and adolescent patients with an usual uncompromised immunologic status. As clinical and radiologic features are not specific, the differential diagnosis to other mandibular diseases is difficult. We report on a case of African histoplasmosis that involved the right mandibula of a 17-year-old Congolese boy with a persistent and fungiform cutaneous ulceration. As mycologic tests had not been carried out initially, the disease was histologically diagnosed on the basis of the presence of numerous intra-cytoplasmic large yeasts in a granulomatous lesion containing giant cells. As it is impossible to confront the histologic diagnosis with mycologic tests in such a situation, the problems of the differential diagnosis to other deep fungus infections and to some yeast-like foreign body-granulomas encountered at the microscopical level underline the importance of culturing organisms from lesions to confirm the histologic diagnosis. It is worth considering this pathology at least for three reasons: it usually mimicks a malignant jaw tumor; it may constitute a migrant pathology; and prognosis is commonly favorable with amphotericin B treatment.