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Although large lesions of the limbs can easily be biopsied without image guidance, lesions in the spine, paraspinal area and pelvis are difficult to target, and benefit from CT guidance to improve the accuracy of targeting the lesion for biopsy purposes. A prospective study of CT-guided core needle biopsies for deep-seated musculoskeletal lesions was conducted at a referral cancer institute over a 4-year period with the aim of assessing the safety and efficacy of the procedure.From January 2000 to December 2003, 136 consecutive CT-guided biopsy sessions were undertaken for musculoskeletal lesions in 128 patients comprising 73 males and 55 females. The following data was recorded in all patients: demographic data, suspected clinicoradiological diagnosis, data related to core biopsy session (date, site, approach, total time required in minutes, number of cores, surgeon satisfaction with adequacy of cores), patient discomfort, complications, histopathology report and number of further sessions if material obtained during the first biopsy session was not confirmatory. The sample obtained during the biopsy session was considered inconclusive if, in the opinion of the pathologist, inadequate or non-representative tissue had been obtained. The diagnosis was considered inaccurate if the final histopathological diagnosis did not match with the biopsy diagnosis, or if subsequent clinicoradiological evaluation at follow up did not correlate with the biopsy diagnosis in those patients who were treated with modalities other than surgery.In 121 patients, a single session was sufficient to obtain representative material, whilst for six patients two sessions, and for one patient three sessions were necessary. The time taken for biopsy, including the pre-biopsy CT examination time, varied from 15 min to 60 min (median 30 min). For 110 bony lesions 116 sessions were required, and for 18 soft-tissue lesions 20 sessions were required. 108 biopsy sessions yielded a diagnosis, whilst 28 were inconclusive (diagnostic yield of 79.41%). Of 108 diagnostic biopsies, five were considered inaccurate (accuracy rate of 95.37%). The overall diagnostic yield and accuracy rate for bony lesions were 81.03% and 95.74%; and those for soft-tissue lesions were 70% and 92.85%. There were two complications with no permanent sequelae.CT-guided core needle biopsy is a safe, easy, and effective technique for the evaluation of deep-seated musculoskeletal lesions, with a high rate of diagnostic yield and accuracy. It facilitates definitive therapy without the patient having to undergo a major surgical procedure for diagnosis.