Concomitant nasal zygomycosis and pulmonary aspergillosis was diagnosed in a 3-mo-old female American bison calf (Bison bison) in Pennsylvania (USA). Etiologic diagnosis was made by immunohistochemistry using a panel of monoclonal antibodies and heterologously absorbed polyclonal antibodies. In the lungs fungal infection was accompanied by hemorrhage, fibrin exudation, and infiltration with neutrophils. Fungi were observed to penetrate apparently normal epithelial lining of the nasal turbinates, and there was hemorrhage, edema, and invasion of blood vessels in the submucosa. In vessels fungi were typically associated with thrombosis. The calf may have been infected due to a high level of exposure to mouldy feed and litter in the environment in combination with a collapse of it's natural defence mechanisms.