A 53-year-old man presented with fever, 15 kg weight loss, ECOG performance status 0, and 12 × 9.5 cm renal tumor with an associated level II (near level III) tumor thrombus extending into the vena cava. We offered a presurgical targeted therapy to downsize the thrombus and primary tumor, which may reduce the extent of the surgery and operative risk. The patient accepted this approach with administration of sorafenib, resulting in a marked reduction of the primary renal tumor and 43% regression in tumor thrombus. Tumor shrinkage and regression of the thrombus allowed resection of the left kidney. Pathological findings revealed that part of the tumor was necrotic tissue. Two years after initiation of presurgical sorafenib therapy, the patient remains alive without evidence of disease progression. Copyright © 2011 S. Karger AG, Basel.