Fast-scan CT is widely and frequently used to guide fine-needle aspiration biopsy (FNAB) of questionable lung nodules. To investigate technical problems, complications, diagnostic accuracy and indications of this technique, the findings were reviewed relative to 118 patients with negative transbronchial biopsy and sputum cytology who underwent CT-guided FNAB of solitary lung lesions. Over a 25-month period, 73 men and 45 women underwent CT-guided FNAB of lung lesions. The CT unit was a GE 9800; 22-gauge 7/9-cm spinal needles were used in most cases, while 22-G 15-cm Chiba needles were used in 6 cases. In 114 patients one FNAB was performed, 4 patients only requiring the maneuver to be repeated. Regarding the malignant nature of the lesions, there were 70 true positive, 36 true negative, 12 false negative and no false positive cytologic findings; sensitivity was 85.36%, specificity and positive predictive value were 100%, negative predictive value was 75% and diagnostic accuracy 89.83%. Only minor complications occurred: 5 cases of hemophtoe, 7 of peripheral bleeding, 4 of chest pain, 4 vagal reactions and 10 cases of pneumothorax, only one of them requiring drainage. In our experience, only one pass per patient is required and the presence of the cytopathologist is unnecessary, since in most of our cases (114/118) the diagnosis was made at the first FNAB performed by the radiologist. CT allowed the lesions to be approached easily and precisely, which is useful especially in small, peripheral or hilar, nodules missed or poorly defined by radiology. To conclude, CT-guided transthoracic FNAB can be suggested as the method of choice to diagnose lung lesions which are difficult to puncture endoscopically because of size or location, and in suspected metastases. Moreover, FNAB can be used as second-line method in the lesions where endoscopic biopsy cannot be performed or whose findings are negative.