Pulmonary carcinoma was diagnosed in an 18 -year-old captive female great horned owl (Bubo virginianus). The owl presented with a history of progressive weakness and sudden onset of frank blood in the droppings. On physical examination, the owl had multiple white to yellow plaques in the oral cavity, decreased air sac sounds on the right side, dyspnea (during manual restraint), and reduced pectoral musculature. Whole-body radiographs revealed obliteration of the right-sided air sacs, a soft tissue plaque/density in the left caudal thoracic air sac, soft tissue opacity over the coelomic organs, and increased medullary opacity in the distal right humerus. The owl died during anesthetic recovery, and the body was submitted for necropsy. Although the clinical signs, physical examination results, radiographic signs, and gross pathology supported a diagnosis of mycotic infection, such as aspergillosis, histopathology confirmed pulmonary carcinoma with metastases to the air sacs and humerus.