OBJECTIVE To evaluate the diagnostic accuracy of transthoracic needle biopsy (TNB) in patients being treated for cancer in order to compare results from small and large pulmonary nodules and to study the efficiency of pathology versus cytology analysis. METHODS 141 consecutive CT-guided TNBs were performed in 134 patients. Cancer had been diagnosed in all cases. From the CT images, nodules were classified as small (< or = 15 mm) (n = 63; 47%) or large (> 15 mm) (n = 71; 53%). RESULTS There were 16 benign and 118 malignant lesions (92 metastasis, 18 primary, 8 unspecified). There was no statistically significant difference for sensitivity and for prevalence of pneumothorax between small or large nodules. For the 107 true-positive and 16 true-negative results, the cytology examination was positive alone in 41 cases (33.3%), the pathology examination in 24 cases (19.5%) and both in 58 cases (47.2%). CONCLUSIONS The diagnostic efficiency of CT-guided transthoracic needle biopsy is as good for small pulmonary nodules (> or = 15 mm) as for larger lesions. This technique is particularly useful in the diagnosis of secondary lesions and does not increase the risk of complications, even in case of small nodules. Ordering both pathology and cytology examinations improves the efficacy of TNB.