We retrospectively analyzed 542 proven/probable mould infections registered, in the course of 2 studies, in 8,633 patients with acute leukemia, focusing on scedosporiosis. We aimed to define scedosporiosis incidence and mortality rate over a 15-year period. Only 5 cases of scedosporiosis were identified, all of them involving patients with acute myeloid leukemia (AML). We also reviewed all cases of Scedosporium spp. infections in acute leukemia reported to date in the international literature. The 52 cases analyzed confirmed that acute myeloid leukemia is the category with the highest risk of scedosporiosis. Clinical features of scedosporiosis were extremely variable and closely related to patient immune status. Infection disseminated to multiple sites in a very high percentage of patients and outcome was confirmed to be very poor. In our surveys all patients died, in spite of Amphotericin B compounds or voriconazole administration. Our review of literature found scedosporiosis attributable mortality rate (AMR) to be 77%. In conclusion, scedosporiosis, although extremely rare, represents a big problem for clinicians because of its aggressive clinical presentation and the lack of an effective therapy. New drugs with in vitro activity against Scedosporium spp (voriconazole, posaconazole) should be considered. However, their clinical activity should be more widely demonstrated.