PURPOSEWe aimed to evaluate whether rapid kV-switching dual energy CT (rsDECT) can discriminate between papillary renal cell carcinoma (RCC) and benign proteinaceous cysts (BPCs) based on iodine and water content.METHODSTwenty-four patients with histopathologically proven papillary RCC and 38 patients with 41 BPCs were retrospectively included. Patients with BPCs were eligible for inclusion when the cysts were stable in size and appearance for at least 2 years or proved to be a cyst on ultrasound or MRI. All patients underwent delayed phase (70–90 s) rsDECT. Iodine and water content of each lesion was measured on the workstation.RESULTSOf papillary RCC patients, 4 (16%) were female and 20 (84%) were male. Mean tumor size was 39±20 mm. Mean iodine and water content was 2.08±0.7 mg/mL and 1021±14 mg/mL, respectively. Of BPC patients, 9 were female and 29 were male. Mean cyst size was 20±7 mm. Mean iodine and water content was 0.82±0.4 mg/mL and 1012±14 mg/mL, respectively. There were significant differences between iodine and water contents of papillary RCCs and BPCs (P < 0.001). The best cutoff of iodine content for differentiating papillary RCC from BPC was 1.21 mg/mL (area under the curve [AUC]=0.97, P < 0.001, sensitivity 96%, specificity 88%, positive predictive value [PPV] 82%, negative predictive value [NPV] 97%, accuracy 91%,); the best cutoff of water content was 1015.5 mg/mL (AUC=0.68, P = 0.016, sensitivity 83%, specificity 56%, PPV 52%, NPV 85%, accuracy 66%).CONCLUSIONAn iodine content threshold of 1.21 mg/mL accurately differentiates papillary RCC from BPCs on a single postcontrast rsDECT. Despite having a high sensitivity, water content has inferior diagnostic accuracy.