Objective To explore the surgical treatment strategies of tumors involving the upper renal segment of inferior vena cava from different histological origins. Methods The clinical data of 32 renal cell carcinoma patients with inferior vena cava tumor thrombus, 11 patients with primary leiomyosarcoma of inferior vena cava and 8 patients with inferior vena cava leiomyomatosis were collected from Changhai Hospital of Naval Medical University (Second Military Medical University) from Jan. 2008 to Apr. 2018. There were 20 males and 31 females, with an average age of (50.1±12.8) (ranged 26-76) years. All patients were confirmed by pathology and underwent open or laparoscopic surgery. Results Fifty patients received surgical resection and 1 surgery was terminated. Of the 32 patients with inferior vena cava tumor thrombus, 30 received thrombectomy and 2 received resection of the inferior vena cava (1 case of right renal cell carcinoma with tumor thrombus did not receive reconstruction of the inferior vena cava, and 1 case of the left renal cell carcinoma with tumor thrombus underwent reconstruction of the inferior vena cava). Of the 11 patients with primary leiomyosarcoma of inferior vena cava, 6 received complete resection of the inferior vena cava and the inferior vena cava was replaced by artificial blood vessel, 4 received partial resection of the invaded inferior vena cava and the inferior vena cava was sutured for reconstruction, and 1 surgery was terminated after intraoperative exploration. Eight patients with inferior vena cava leiomyomatosis did not undergo resection or reconstruction of the inferior vena cava. At a median follow-up of 17 months (ranged 1-36 months), the survival rates of the 3 groups were 84.4% (27/32), 63.6% (7/11) and 100.0% (8/8), respectively. Four cases died during the perioperative period, including 2 cases of renal cell carcinoma with thrombus shedding during operation, 1 case of renal cell carcinoma with inferior vena cava tumor thrombus and 1 case of inferior vena cava leiomyosarcoma resulted in hepatic congestion and postoperative disseminated intravascular coagulation. Five cases died of tumor metastasis during follow up. Conclusion There were significant differences in demography, vascular invasion, shedding risk of cancer/tumor thrombus and prognosis among patients with renal cell carcinoma with inferior vena cava tumor thrombus, primary leiomyosarcoma of inferior vena cava and inferior vena cava leiomyomatosis. Preoperative comprehensive evaluation of the patient's condition can be helpful, but there is no effective method to assess the difficulties of surgery preoperatively or to avoid the shedding of cancer/tumor thrombus and severe postoperative complications.