Abstract This case report describes an uncommon manifestation of histoplasmosis on the soft palate. The importance of appropriate treatment and follow-up in complex cases is emphasized, especially in patients with chronic diseases. Oral lesions may occur as multiple, granular and painful ulcers, as well as verrucous growths. Lesions may also be deep, with infiltrative edges and erythematous or with white areas, accompanied by local lymphadenopathy, resembling a carcinoma on clinical examination. In this sense, a fast and accurate diagnosis is essential to the success of treatment of oral histoplasmosis.