An increasing number of renal masses with heterogeneous histology and clinical behavior are being detected with modern abdominal imaging. We provide an analysis of the rationale, indications, technique, safety, and outcomes of percutaneous needle core biopsies of renal tumors. Renal tumor biopsies can be performed under ultrasound or CT guidance with local anesthesia in the majority of cases. Core biopsies using 18G needles with a coaxial technique should be favored to sample solid renal masses. With the use of modern techniques biopsies are safe, with limited risk of significant bleeding and virtually no risk of tumor seeding. Both diagnostic yield and accuracy for tumor malignancy and histotype are good in centers with expertise. Renal tumor biopsies should be increasingly performed in the diagnostic work-up of renal masses that are indeterminate at imaging, for the histological characterization of small renal masses in patients who are candidates for non-surgical management in order to support treatment decisions, after thermal ablation in order to confirm histological success and monitor for recurrence, and in metastatic tumors when a cytoreductive nephrectomy is not indicated in order to select the best suited targeted therapy. Well-designed, prospective, large studies are needed to define optimal and standardized patterns of biopsy and further improve the accuracy of biopsies to determine tumor histology. Molecular and genetic analyses of biopsy specimens have the potential to provide additional information to support patient counseling and treatment decision-making.