Scedosporium prolificans, a hyaline filamentous fungus, is widely distributed in the environment and is currently an emerging human pathogen, especially among immunocompromised patients. However, S. prolificans endocarditis is rare. We herein report a case of S. prolificans endocarditis in a 64-year-old patient with breast cancer in complete remission for 30 years after chemotherapy and radiation treatment who was not cured. Susceptibility testing showed resistance to all antifungal drugs, except echinocandin. A review of the literature revealed 10 cases of S. prolificans endocarditis; of these, only one involved an immunocompetent host with no risk factors and only two patients survived. In order to improve the mortality rate, it is necessary to establish rapid diagnostic methods and efficient therapeutic approaches.