Background: RECIST is a standard tool for tumor response assessment. However, evaluation for targeted therapy by RECIST is insensitive because tumors often showed a modest change in size despite of significant necrosis. Therefore, we investigated an impact of contrast enhancement reduction for tumor shrinkage in RCC patients with presurgical targeting therapy. Methods: From March 2011 to July 2015, 17 patients (18 tumors) with RCC who underwent presurgical targeting therapy were included. Indications for presurgical targeting therapy were cT3-4, bilateral tumors, poor performance status, or small distant metastasis. Contrast enhancement reduction was evaluated by contrast medium enhanced area (CMEA) before and after targeting therapy. CMEA measurements were performed by OsiriX and Adobe Photoshop. Eighteen tumors were evaluated by RECIST and CMEA. Differences between two methods were compared. Results: Median age and followup after initiation of targeted therapy were 68 years old and 15.3 months. IVC thrombus and small distant metastasis existed in seven (41%) and five (29%) patents, respectively. Fifteen patients (88%) received TKI based (sunitinib and/or axitinib), and three patients (12%) received mTOR inhibitor based (everolimus or temsirolimus) presurgical therapy. The median treatment period of presurgical targeted therapy was 3.3 months. Median tumor responses in RECIST and CMEA were 10.5% and 49.0%, that was significantly correlated by liner regression analysis (P = 0.002). TKI based presurgical therapy showed significant tumor reduction in CMEA than RECIST (P = 0.0062). In addition, tumor reduction rate was significantly higher in TKI based presurgical therapy than mTOR inhibitor (P = 0.014). No patient experienced tumor recurrence. Conclusions: Contrast enhancement reduction might be useful tool for tumor shrinkage in patients with RCC who underwent presurgical targeting therapy.