OBJECTIVES: To define the preoperative independent predictors indicating that renal mass has benign histologic features. METHODS: A total of 1664 patients with Stage T1-T2N0M0 with a unilateral renal mass underwent nephrectomy. The endpoint at multivariate analysis was benign versus malignant histologic features. RESULTS: The surgical approach (odds ratio [OR] 2.9, P = .0001), sex (OR 1.97, P = .0001), and age (OR 1.01, P = .007) were independent predictors for the malignant-benign distinction. Malignant tumors were more likely to occur in men (878 of 1009, 87%) versus women (515 of 651, 79%; P <.001). A weak relationship was found between an increasing tumor size and malignancy risk in men only. High-grade renal cell carcinoma was more prevalent in men (31% versus 21%, P = .001). The histologic tumor types were distributed differently between the 2 sexes: 8% papillary renal cell carcinoma in women versus 16% in men, 86% and 78% clear cell renal cell carcinoma, 33% and 57% oncocytoma, and 40% versus 12% angiomyolipoma, respectively. The physician's preoperative judgment regarding tumor amenability for nephron-sparing surgery resulted in patient selection: 10% benign tumors for radical nephrectomy versus 25% for partial nephrectomy (P = .001) and 31% versus 20% high-grade tumors, respectively (P = .0001). CONCLUSIONS: Renal tumors were consistently benign in 20% of women, regardless of size. In contrast, in men, the malignancy risk increased slightly with tumor size. The surgeons' preoperative decision regarding nephron-sparing surgery caused a selection bias in favor of benign lesions, regardless of sex. Our findings support the possibility of basing treatment decisions on the preoperative biopsy findings. Such changes could alter current practice and limit treatment of histologically proven benign lesions to surveillance or ablation only.