The biopsy of a musculoskeletal lesion is an important event, the outcome of which guides patient management and helps determine patient prognosis. The principles of biopsy include complete radiologic staging before the biopsy, thorough prebiopsy planning including consultation with the pathologist and radiologist, determining the most appropriate method of biopsy (fine needle, core needle, open surgical biopsy), placing the biopsy tract appropriately, and making sure the biopsy tract can be removed at the time of resection, avoiding contamination of uninvolved structures, avoiding transverse incisions, preventing pathologic fracture, handling biopsy tissue appropriately, and considering referral before biopsy. The common errors of biopsy include sampling errors, postbiopsy hematomas, the use of transverse incisions, tumor implantation, and the treatment of an unsuspected sarcoma with prophylactic fixation. Thoughtful prebiopsy planning and careful completion of the biopsy can result in an expedient and accurate diagnosis. If the treating physician lacks significant expertise in performing biopsy and management of patients with musculoskeletal lesions, then referral to a musculoskeletal oncologist before biopsy should be considered.