Introduction <p>Histoplasmosis is a fungal infection caused by <i>Histoplasma capsulatum</i>, which is endemic in several countries, including Brazil. Disseminated histoplasmosis is a severe manifestation caused by the systemic spread of the infection. It usually occurs in immunocompromised patients, particularly in individuals with HIV infection and transplant recipients, but few reports have described cases in immunocompetent individuals.</p> Case Presentation <p>This report describes a case of disseminated histoplasmosis with oral and intestinal manifestations in a non-HIV patient with a history of alcohol abuse, hepatitis B, lymph node, and pulmonary tuberculosis, but no known risk factor for disseminated histoplasmosis. At physical examination, the patient presented with bilateral submandibular lymphadenopathy. A chest radiograph revealed a diffuse micronodular infiltrate with bilateral hilar and right paratracheal lymph node enlargement. Histopathological analysis of oral lesion confirmed the diagnosis of chronic and active ulcerated mucositis associated with a fungal infection suggestive of histoplasmosis. Due to a previous history of intestinal histoplasmosis with incomplete treatment, colonoscopy and intestinal biopsy were performed and confirmed gastrointestinal involvement by disseminated histoplasmosis. Treatment with intravenous amphotericin B followed by itraconazole maintenance therapy resulted in complete regression of the oral lesion and clinical improvement of the gastrointestinal manifestations.</p> Conclusions <p>This case report contributes to the clinical data on histoplasmosis in non-HIV patients and helps clarify its diagnosis in immunocompetent individuals or those with unclear immunosuppression status.</p>