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Alternaria spp. have emerged as opportunistic pathogens particularly in immunosuppressed patients, such as bone marrow transplant recipients. The authors present a case of Alternaria alternata in a patient with Fanconi's anemia, who received antifungal prophylaxis with posaconazole after an unrelated bone marrow transplantation, followed by empirical antifungal treatment with caspofungin when persistent fever emerged until cutaneous lesions eventually appeared. At that time there were clinical reasons to assume that the patient had an infection with an emerging fungus. This consideration triggered a change of the antifungal therapy from caspofungin to liposomal amphotericin B. After collecting sufficient evidence for the presence of an invasive fungal infection by A. alternata and given the severity of neutropenia and other immunosuppression, oral posaconazole was added to liposomal amphotericin B. The course of disease in this case suggests a possibly synergistic interaction between liposomal amphotericin B and posaconazole when administered simultaneously to treat an invasive systemic infection by Alternaria spp. in immunocompromised patients.