To evaluate the utility of imaging-guided fine-needle percutaneous biopsy of renal masses, we conducted a prospective analysis of our imaging-guided procedures from January 1999 to February 2003. We performed 54 percutaneous core biopsies in 46 patients. Fluoro-computed tomography and ultrasound guidance were respectively used in 48 and six cases. One to four specimens were obtained by using an 18-gauge automated coaxial biopsy system. We reviewed the patients medical records, pathology results, and imaging studies. Core biopsy results were compared with surgical pathology (n=27) or clinical follow-up (n=19). All biopsies provided sufficient material for analysis. The mean tumor size was 33 mm. Biopsy findings were positive for malignancy in 31 cases; histologic diagnoses included renal cell carcinoma (n=23), transitional cell carcinoma (n=5), and metastasis (n=3). Biopsy revealed 15 benign diagnoses: oncocytoma (n=6), hemorrhagic renal cyst (n=3), chronic nephritis (n=3), angiomyolipoma (n=2), and mycotic renal abscess (n=1). The average follow-up period for patients with benign diagnoses was 16 months. Biopsy results showed normal renal parenchyma in eight of 54 procedures, all of which had recuperated by subsequent biopsies. No immediate complications occurred after the procedures. Imaging-guided percutaneous core biopsy is a safe and accurate method for the evaluation of renal masses.