© American Roentgen Ray Society. OBJECTIVE. The purpose of this study was to assess the diagnostic accuracy of effective atomic number maps reconstructed from dual-energy contrast-enhanced data for discriminating between nonenhancing renal cysts and enhancing masses. MATERIALS AND METHODS. Two hundred six patients (128 men, 78 women; mean age, 64 years) underwent a CT renal mass protocol (single-energy unenhanced and dual-energy contrast-enhanced nephrographic imaging) at two different hospitals. For each set of patients, two blinded, independent observers performed measurements on effective atomic number maps from contrast-enhanced dual-energy data. Renal mass assessment on unenhanced and nephrographic images, corroborated by imaging and medical records, was the reference standard. The diagnostic accuracy of effective atomic number maps was assessed with ROC analysis. RESULTS. Significant differences in mean effective atomic numbers (Zeff) were observed between nonenhancing and enhancing masses (set A, 8.19 vs 9.59 Zeff; set B, 8.05 vs 9.19 Zeff; sets combined, 8.13 vs 9.37 Zeff) (p < 0.0001). An effective atomic number value of 8.36 Zeff was the optimal threshold, rendering an AUC of 0.92 (95% CI, 0.89-0.94), sensitivity of 90.8% (158/174 [95% CI, 85.5-94.7%]), specificity of 85.2% (445/522 [95% CI, 81.9-88.2%]), and overall diagnostic accuracy of 86.6% (603/696 [95% CI, 83.9-89.1%]). CONCLUSION. Nonenhancing renal cysts, including hyperattenuating cysts, can be discriminated from enhancing masses on effective atomic number maps generated from dualenergy contrast-enhanced CT data. This technique may be of clinical usefulness when a CT protocol for comprehensive assessment of renal masses is not available.