Aim : To describe various approaches of computed tomography (CT)-guided core biopsy and evaluate its ability to obtain adequate tissue for the assessment of mediastinal masses. Materials and Methods : Between February 2004 and October 2006, 83 percutaneous CT-guided biopsies of mediastinal lesions were performed on 82 patients under local anesthesia. Coaxial needles were used and minimum of 3-4 cores were obtained. Post-biopsy CT scan was performed and patients observed for any complications. Tissue samples were taken to Pathology Department in formalin solution. Results : From the 83 biopsies, adequate tissue for histological diagnosis was obtained in 80 (96%), and the biopsy was considered diagnostic. Of the 80 diagnostic biopsies, 74 biopsy samples were definitive for neoplastic pathology and 6 biopsy samples revealed no evidence of malignancy. There were no major complications. Minor complications were recorded in 5 patients. Conclusion : Percutaneous image-guided core biopsy of mediastinal lesions is an accurate, safe and cost-effective tool for the initial assessment of patients with mediastinal masses.