CT-guided transthoracic needle biopsy is a well-established method for diagnosing pulmonary lesions. However, despite extensive literature on the subject, many aspects of the procedure remain unexamined in large controlled trials. Consequently, practices vary across centers due to differences in local facilities, operators' preferences, and experience. This article summarizes the essential steps of CT-guided transthoracic needle biopsy, covering patient selection to technical tips and tricks, complication management, and rapid onsite cytology evaluation. The techniques described here are based on years of clinical practice, research findings, and close collaboration with colleagues from various specialties, aiming to maximize tissue retrieval while minimizing complications. Moreover, given the growing importance of molecular analyses in the diagnosis and management of lung cancer, this article provides a concise and practical guide on proper biopsy specimen handling.