This report describes the first case of cerebral aspergillosis in a heart transplantation patient caused by Aspergillus ustus and reviews 15 previously reported cases of invasive aspergillosis in immunocompromised hosts caused by this mold. The utility of molecular analysis for the identification of unusual fungal pathogens is also described. The refractory nature of A. ustus to treatment is similar to other Aspergillus species and treatment options are reviewed.