Histoplasmosis is an infection caused by the dimorphic Histoplasma capsulatum fungus. Oral histoplasmosis is usually a manifestation of disseminated histoplasmosis, which occurs when hematogenously disseminated organisms cannot be contained by the individual's immune system, either following primary infection or as a reactivation of disease. Rarely, oral histoplasmosis can represent primary localized disease.

Exposure may occur in regions such as the Central and Eastern United States, especially the Ohio and Mississippi River Valleys. Cases have also been reported in Central and South America, Africa, Asia, and Europe.

Oral histoplasmosis typically manifests as one or more tender intraoral nodules or ulcers with dysphagia and/or odynophagia. Fever, weakness, weight loss, lymphadenopathy, and hepatosplenomegaly frequently accompany oral histoplasmosis in immunocompromised patients; however, in some cases, patients appear well. Oral findings may also predate the onset of systemic symptoms and signs.

Predisposing factors include immunosuppression (including HIV, organ transplant, renal failure, and prolonged use of systemic corticosteroids and other immunosuppressants, including tumor necrosis factor alpha antagonists) and advanced age. Although the organisms are most commonly present in bird and bat excrement, patients frequently do not recall a definitive exposure.