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Leiomyosarcoma of the inferior vena cava is a rare smooth muscle sarcoma with a variable presentation. We report a case of inferior vena cava leiomyosarcoma with the sole presenting symptom of lower extremity edema, with an initial diagnosis of deep venous thrombosis. Further evaluation with a venogram and computed tomography scan of the patient’s abdomen and pelvis revealed a wall-adherent filling defect and soft tissue mass and subsequent biopsy revealed leiomyosarcoma of her inferior vena cava. Our patient was treated with a thrombectomy and excision of her tumor and was then provided chemotherapy as an outpatient with resolution of her symptoms. Such a case demonstrates a rare underlying etiology of the common presenting symptom of lower extremity edema.