Percutaneous image-guided biopsy of renal masses is a safe and accurate procedure. Although once reserved for the diagnosis of unresectable renal cell carcinoma, metastases, lymphoma, and infection, today percutaneous image-guided biopsy has an expanded role. There is increasing awareness that a substantial proportion of small, solid renal masses are benign neoplasms. Although imaging can be used to diagnose most of them, some are incorrectly believed to represent renal cell carcinoma and unnecessary surgery may be performed. Based largely on advances in cytological techniques, percutaneous biopsy can be now be used to diagnose benign neoplasms and thus prevent them from being treated unnecessarily. Concurrent advances in percutaneous ablation have also promoted its use. As a result, there are 8 established indications for percutaneous biopsy, and reason to believe that the number of indications will expand further in the future.