Computed tomography, though few previous reports have dealt with this aspect of it, is an excellent aid when percutaneous skeletal biopsies have to be taken, especially in critical skeletal regions. Our own series consists of 48 CT-guided musculoskeletal biopsy procedures, mainly concerning the spine and pelvis. We used biopsy needles with calibers between 22 G and 14 G; specifically, the sure-cut needle was used in most cases. There were no complications. The results were conclusive in 29 cases, semiconclusive in 10 cases, and inconclusive in 9 cases. The advantages of CT guidance are most obvious in the case of lesions of the axial skeleton and pelvis: it allows precise planning of an adequate biopsy approach, better location of small cortex leaks for intraosseous entry of the puncture needle, and more sensitive selection of the best place for tissue sampling. Therefore, with CT guidance intraosseous lesions are more accessible, even to less highly invasive instruments. The risk of complications is low, and the accuracy similar to that obtained with fluoroscopic guidance.