Oral involvement is rarely found in histoplasmosis, except in its disseminated form, which is mostly observed in the severely immunocompromised host. Herein, we presented the case of a 36-year-old female with a previous history of liver transplant, who was hospitalized due to fever, chills, night sweats, diarrhea, and painful oral lesions over the last 3 days. The oral examination revealed the presence of painful shallow ulcers lined by a pseudomembrane in the gingiva and the soft and hard palate. The initial working diagnosis comprised cytomegalovirus reactivation or herpes simplex virus infection. The diagnostic work-up included incisional biopsies of the gingiva and the sigmoid colon. Both biopsies confirmed the diagnosis of histoplasmosis. Intravenous itraconazole was administered with significant improvement after 7 days. Although oral involvement is rare, histoplasmosis should be included in the differential diagnosis of oral lesions, particularly when the patient is immunosuppressed. This study reports a rare presentation of histoplasmosis involving the mucosa of the oral cavity and the colon.