Scedosporium apiospermum is a mold that is increasingly being recognized as an opportunistic pathogen in immunocompromised patients, and treatment is complicated by intrinsic resistance to several antifungal agents. In our hospital, two cases of S. apiospermum infection occurring within 2 weeks were successfully treated with voriconazole. Since both patients were infected with an uncommon pathogen, a search for a common nosocomial source was performed. As environmental cultures yielded no S. apiospermum, and random amplified polymorphic DNA (RAPD) fingerprinting showed that the patients' strains were genotypically unrelated, we considered a common nosocomial source of S. apiospermum to be unlikely.