OBJECTIVE. The purpose of this article is to provide a step-by-step guide for bone imaging-guided percutaneous core needle biopsy, including the armamentarium available and the most recent advances. CONCLUSION. Bone imaging-guided percutaneous core needle biopsies are well-established, minimally invasive, cost-effective interventions for histologic characterization of bone lesions with an excellent safety profile and diagnostic outcomes; they play a crucial role in management of patients. Radiologists involved in the care of patients with bone lesions must be familiar with the various steps involved in such procedures and their role in patient management.