The frequent occurrence of the oral lesions of histoplasmosis in combination with disseminated infection necessitates prompt recognition and diagnosis. The possibility of such an infection occurring in an immunocompromised patient should be considered high on the list of differential diagnoses, and treatment should be planned accordingly. The varied clinical presentations of histoplasmosis, ranging from shallow ulcers to nodular or vegetative masses, can be confusing and may lead to inaccurate diagnosis with resultant delay in treatment or inappropriate treatment. Submission of adequate tissue sections for microbiological and histopathological assessments is crucial.