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To assess the feasibility, image quality, and radiation dose of computed tomography (CT) renal perfusion imaging in the adaptive 4-dimensional (4D)-spiral mode in patients with renal cell carcinoma (RCC), and to compare quantitative measurements between 2-dimensional regions-of-interest (2D-ROI) and 3-dimensional volumes-of-interest (3D-VOI).Twenty-one patients (13 male; age, 67.4 ± 9.5 years) with 24 histologically proven RCCs underwent CT perfusion imaging (100 kV, 100 mAs/rotation, scan range 10 cm, examination time 40.17 seconds) in a 4D-spiral mode with dual-source 128-slice CT. The ability to suspend respiration during CT perfusion imaging was visually monitored. Two independent readers assessed motion artifacts of CT perfusion imaging data sets on a 4-point scale before and after automated motion correction. Qualitative (enhancement pattern) and quantitative perfusion analysis (blood flow [BF], blood volume [BV], flow extraction product [KTrans]) were performed in the tumor and in healthy ipsi- and contralateral renal cortex applying the maximum-slope and a modified Patlak approach for quantitative analysis in 2D-ROI and 3D-VOI, the latter including the entire RCCs.Of the 21 patients, 8 (38%) could suspend respiration throughout the perfusion scan. Of 21 RCCs, 18 (86%) were completely included in the scan range. Motion artifacts were significantly reduced after automated motion correction (P < 0.001). All 24 RCCs could be included in the qualitative perfusion analysis, and 22 of 24 (92%) were eligible for quantitative perfusion analysis. Enhancement was homogenous in 4 (17%), peripheral in 4 (17%), and heterogeneous in 16 (66%) tumors (good interobserver agreement, κ=0.74). A high correlation was found between the 2 readers regarding quantitative perfusion parameters (r=0.93–0.94, P < 0.01). Quantitative measurements in 3D-VOIs revealed significantly lower BV, BF, and KTrans in RCCs than in normal renal cortex (P < 0.001). In solid tumor periphery, BV was similar to the renal cortex (P=0.299), while BF and KTrans were significantly lower (P < 0.01 and <0.001) in tumor tissue. Comparison of tumor measurements in 3D-VOIs with those obtained from 2D-ROIs revealed considerable differences in perfusion parameters beyond the 95% confidence limits in 46% to 68% of the tumors. KTrans was significantly higher in the contralateral than in healthy ipsilateral renal cortex (P < 0.01). Estimated effective radiation dose of the CT perfusion protocol was 16.3 mSv.CT perfusion imaging using an adaptive 4D-spiral mode is feasible and enables, after use of automated motion correction, the reliable analysis of renal perfusion in patients with RCCs. Considerable tumor heterogeneity was found, with differences in perfusion parameters between 2D-ROI and 3D-VOI analysis, reinforcing the use of volumetric techniques for perfusion imaging and analysis. Differences between ipsi- and contralateral healthy renal cortex KTrans suggest a compensatory increase in glomerular filtration rate in the healthy contralateral kidney.