Percutaneous biopsies of musculoskeletal lesions are a safe, economical, and reliable method of obtaining a diagnosis. Most of these biopsies are done under CT guidance, but fluoroscopy is an alternative. Conditions that can be discovered through percutaneous biopsies include metastases, primary benign tumors, infection, and metabolic disease. Experience with invasive procedures and with imaging equipment are the requirements for a physician interested in performing these biopsies.