Purpose To retrospectively determine if homogeneous high T1 signal intensity (SI) masses with smooth borders on unenhanced magnetic resonance (MR) images can be characterized as benign. Materials and Methods Institutional review board approval was obtained for this HIPAA-compliant retrospective study, with waiver of informed consent. MR images in 84 patients with hemorrhagic or proteinaceous cysts and 50 patients with renal cell carcinoma (RCC) were evaluated. Sixty-three cysts and 49 RCCs underwent unenhanced computed tomography (CT). SI ratio and CT attenuation were determined. Two radiologists evaluated lesions as follows: score 1, homogeneous with smooth borders; score 2, mildly heterogeneous with mildly lobulated borders; score 3, moderately heterogeneous and irregular borders; and score 4, markedly heterogeneous with markedly irregular borders. Statistical analysis was performed by using multivariable logistic regression, Welch t test, Z test, Fisher-exact test, Shapiro-Wilk test, and receiver operating characteristic curve analysis. A diagnostic criterion was formulated by using classification and regression tree analysis. Results SI ratio and attenuation of hemorrhagic or proteinaceous cysts were significantly higher than those of RCCs (SI ratio: cyst 2.4 ± 0.8, RCC 1.5 ± 0.3; attenuation: cyst 51.9 ± 21.5, RCC: 34.8 ± 10.0). Reader 1 scored morphology of 68 (81%) hemorrhagic or proteinaceous cysts as score 1 on MR images and as score 45 (71%) on CT scans. Reader 2 scored morphology of 59 (70%) hemorrhagic or proteinaceous cysts as score 1 on MR images and as score 43 (68%) on CT scans. Two-step classification tree suggested that homogeneous high T1 SI lesions with smooth borders and SI ratio of greater than 1.6 predict the lesion as benign cysts. Similar algorithm for CT suggested threshold of 51 HU. Increasing threshold to 2.5 for SI ratio and 66 for Hounsfield units resulted in 99.9% confidence for characterizing benign cysts. Conclusion The retrospective assessment shows that morphologic assessment and SI quantification on unenhanced T1-weighted MR images can be used to differentiate benign hemorrhagic or proteinaceous cysts from RCC, although prospective assessment will be needed to confirm these results. (©) RSNA, 2016.