Fungal endocarditis is associated with severe patient morbidity and mortality. Unfortunately, fungal endocarditis is difficult to diagnose because fungal pathogens are uncommonly isolated from routine blood cultures. Histopathological examination of surgically excised cardiac valves, peripheral emboli and systemic ulcers may be useful in identifying pathogens as etiological agents of culture-negative endocarditis. The authors describe a 63-year-old man who had culture-negative endocarditis. Multiple echocardiograms showed progression of the vegetations with valve stenosis despite treatment with multiple antimicrobials. He had multiple peripheral emboli before surgery. Disseminated histoplasmosis was diagnosed by bone marrow culture. Yeast organisms consistent with histoplasma were shown in the vegetations of his excised mitral valve prosthesis. The patient was treated with amphotericin and has been doing well in the two years since his surgery. The diagnosis and management of fungal endocarditis are emphasized.