Leiomyosarcoma of the inferior vena cava is a rare malignancy, and radical resection with negative margins remains the only hope for cure. In this report we cite four cases of this tumor treated at The University of Texas M.D. Anderson Cancer Center with particular emphasis on the use of preoperative chemotherapy. In our patients, preoperative chemotherapy did not adversely affect operative outcomes or survival. The potential benefits of preoperative chemotherapy include control of micrometastases, reduction in tumor size before resection, and in situ evaluation of tumor response to chemotherapy for postoperative adjuvant therapy.