To prospectively evaluate feasibility and diagnostic performance of the 14-gauge helical-tip (Spirotome (TM), Cook(A (R)) Medical, Bloomington, USA) needle in transthoracic needle biopsy (TTNB) of lung lesions, compared to a conventional 18-gauge Tru-Cut needle. Study was institutional review board approved, with informed consent obtained. Data from synchronous Spirotome and Tru-Cut image-guided TTNB of 20 consecutive patients with malignant peripheral lung tumors larger than 3 cm were enrolled for pathologic characterization and mutational analysis. Samples obtained with Spirotome and Tru-Cut needle were compared for fragmentation, length, weight, morphologic and immunohistochemistry typifying, tumor cellularity (TC) and DNA concentration. The technical success rate for TTNB with Spirotome was 100%, and no major complications occurred. Less fragmentation (mean 2 vs. 3 fragments, P = .418), greater weight (mean 13 vs. 8.5 mg, P = .027) and lower length (mean 10.2 vs. 12.6 mm, P = .174) were observed with Spirotome compared to Tru-Cut needle. Accuracy of Spirotome and Tru-Cut needle in defining cancer histotype was similar (90%). Absolute and relative TC (mean 42 vs. 38, 124 vs. 108/10HPF), and DNA concentration (mean 49.6 vs. 39.0 ng/mu l) were higher with Spirotome compared to Tru-Cut needle, with no statistical significance (P = .787 and P = .140, respectively). Percutaneous 14-gauge Spirotome TTNB of selected lesions is feasible and accurate. It provides adequate samples for diagnosis, comparable to 18-gauge Tru-Cut needle, with a higher amount of tumor tissue (weight, TC, DNA concentration) even in shorter samples.