Accurate diagnosis of spine lesions is important for its successful management. Imaging-guided percutaneous biopsy is gaining increasing acceptance as a means for obtaining tissue for diagnosis. Most biopsies can be rapidly performed under local anaesthesia, with little patient discomfort and improved safety. Spinal anatomy is, however, complex with many adjacent vital structures. Good knowledge of anatomy and precise needling technique is, therefore, important. Today, biopsy of spinal lesions is best performed under computed tomography (CT) fluoroscopic guidance. Indications for imaging-guided biopsy include confirming metastasis in a patient with a known primary tumour, determining the nature of a solitary bone lesion, excluding malignancy in vertebral body compression, and investigating for infection. Among the various issues to be considered are site of lesion, location of adjacent vital structures, approach, and type and size of needle. Complications are rare, particularly when a meticulous technique is applied. In summary, CT-guided percutaneous biopsy is a safe and an effective technique for the evaluation of spinal lesions and useful in planning therapy.