Primary mediastinal leiomyosarcoma is an extremely rare malignancy, and the only opportunity for a cure lies with an aggressive surgical approach. We report a 66-year-old woman who underwent complete resection of a giant mediastinal leiomyosarcoma located on the bilateral diaphragm. The tumor encased the inferior vena cava and compressed the adjacent structures. Using cardiopulmonary bypass with 20 minutes of hepatic ischemia, the tumor was completely resected with combined resection and reconstruction of the surrounding structures. Because of the tumor size and location in the boundary area between thoracic and abdominal surgeries, the procedure necessitated the cooperation of many expert surgeons. (C) 2015 by The Society of Thoracic Surgeons