A technique for biopsy of small or inaccessible mediastinal, hilar, or pulmonary lesions with computed-tomographic (CT) guidance is described. A modified coaxial system was used in order to make multiple passes possible without multiple punctures. The size of the original puncture needle (23 gauge) provided the inherent safety associated with a fine needle. All repositioning was done using this needle and CT until the lesion was engaged. The hub of the needle was then cut, and a 19-gauge needle was inserted coaxially over the larger needle. After removal of the 23-gauge needle, multiple biopsy specimens were then obtained coaxially with a 22-gauge needle through the 19-gauge needle. One small pneumothorax and no bleeding occurred in 10 instances. Results suggest that the combined use of CT guidance and this modified coaxial system may offer an extra margin of safety for difficult cases.