Extramedullary hematopoiesis (EMH) associated with myelofibrosis uncommonly occurs within the thorax. We describe the first reported case of acute and rapidly fatal respiratory failure due to pulmonary interstitial EMH associated with myelofibrosis. Interstitial EMH should be considered in the differential diagnosis of patients with interstitial pulmonary infiltrates and respiratory failure accompanying a disease process known to predispose to the development of EMH.