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Bone, soft-tissue, and articular lesions are often well visualized by magnetic resonance imaging. Our goal was to evaluate the diagnostic performance of magnetic resonance imaging-guided biopsies of selected musculoskeletal lesions.In this retrospective case series, forty-five consecutive biopsies were performed in an open mid-field 0.5-T interventional magnetic resonance imaging unit with a real-time guidance system. The biopsies were performed at twenty bone, eighteen extra-articular soft-tissue, and seven intra-articular soft-tissue sites. The main reasons for using magnetic resonance imaging guidance were the need to improve lesion conspicuity compared with that provided by other imaging modalities, the need for site-specific targeting within the lesion, and the need for real-time guidance. Samples were obtained with fine-needle aspiration, core-needle biopsy, or a combination of these techniques. An independent reference standard was used to confirm the final diagnosis. Diagnostic performance was evaluated on the basis of the diagnostic yield (the proportion of biopsies yielding sufficient material for pathological evaluation) and diagnostic accuracy (sensitivity, specificity, positive predictive value, and negative predictive value). Complications were identified as well.The diagnostic yield was 91% (forty-one of forty-five biopsies yielded sufficient material for a diagnosis) overall, 95% (nineteen of twenty) for the bone lesions, 94% (seventeen of eighteen) for the extra-articular soft-tissue lesions, and 71% (five of seven) for the intra-articular soft-tissue lesions. With regard to the diagnostic accuracy, the sensitivity was 0.86, the specificity was 1.00, the positive predictive value was 1.00, and the negative predictive value was 0.76 in the overall group. The respective values were 0.92, 1.00, 1.00, and 0.86 for the bone lesions; 0.77, 1.00, 1.00, and 0.57 for the extra-articular soft-tissue lesions; and 1.00, 1.00, 1.00, and 1.00 for the intra-articular soft-tissue lesions. There was one complication: exacerbation of neuropathic pain related to a biopsy of a peripheral nerve sheath tumor.Magnetic resonance imaging-guided percutaneous biopsies of musculoskeletal lesions for which other imaging modalities might be inadequate have a good diagnostic performance overall. The performance can be very good for bone lesions, moderate for extra-articular soft-tissue lesions, and fair for intra-articular soft-tissue lesions.Diagnostic Level II. See Instructions to Authors for a complete description of levels of evidence.