The use of percutaneous biopsy of renal masses has not been traditionally widely used because of concerns about safety, accuracy and sampling errors. The current gold standard of treatment for localized renal tumors is partial or radical nephrectomy. However, many small masses are benign tumors or low-grade renal cell carcinomas (RCCs). In selected cases, RCCs can be managed with active surveillance or with minimally invasive ablative technologies. In the setting of metastatic disease, the histological characterization of a renal tumor may also be helpful to select the most suitable targeted treatment. With the development of new and improved techniques and increasing expertise, percutaneous needle core biopsy of renal masses is a safe and accurate diagnostic procedure. Clinically significant bleeding is very rare and no case of RCC seeding along the needle tract has been observed in the last decade. Percutaneous biopsy should have an increasing role in the diagnostic management of renal masses, particularly in elderly or unfit patients diagnosed with small incidental masses or in patients with metastatic disease being considered for cytoreductive surgery and/or therapy with biological modifiers.