This study reports one case of primary inferior vena cava (IVC) leiomyosarcoma. A 67-year-old woman was referred to the authors' clinic for evaluation. She presented complaining of epigastric and right upper abdominal quadrant pain. Contrast-enhanced abdominal computed tomography scan revealed a 5.2 × 6.4 cm heterogeneously enhancing mass involving the anteromedial aspect of the IVC, below the renal vein (segment I), deforming the duodenum. There was a partial intraluminal extension in the IVC. Laparotomic resection was performed, with total en bloc excision of the lower IVC tumor. The caval continuity was restored with concomitant interposition of a banked depopulated vena cava homograft. Histological findings showed leiomyosarcoma originating from IVC. The postoperative course was uneventful: Neither recurrence nor metastasis was evident at 4 years postsurgery.