Background: Percutaneous needle biopsy has many advantages over open biopsy in the treatment of neoplasms. However, the accuracy of needle biopsy in the diagnosis of musculoskeletal lesions has not yet been established. Here, we evaluate the accuracy and limitations of the procedure for musculoskeletal lesions. Methods: The diagnoses of 163 needle biopsies (bone, 91; soft tissue, 72) performed on 157 consecutive patients using a Jamshidi needle or an Ostycut needle for bone lesions, or a Tru-cut needle for soft tissue lesions were compared with the final diagnoses made by open biopsy and/or a definitive operation. Results: One hundred forty-three specimens (88%) were determined to be adequate for histological examination. Obtaining undamaged cores from very hard bony lesions or sclerotic cyst walls proved difficult. A pathologist with experience in musculoskeletal lesions was able to differentiate malignant tumors from benign lesions in 97% of the cases (bone, 100%; soft tissue, 94%) and arrive at a specific diagnosis in 88% (bone, 96%; soft tissue, 78%) when adequate cores were obtained. Differentiating a well-differentiated liposarcoma from a benign lipoma and inflammatory lesions from benign tumorous conditions, was difficult. The overall accuracy was 77% (bone, 85%; soft tissue, 68%). There was no morbidity related to the procedure. Conclusion:The results indicate that needle biopsy is safe and accurate for diagnosing musculoskeletal lesions.