Transthoracic needle biopsy (TNB) of pulmonary nodules requires the skills of two specialists: (1) the radiologist and (2) the pathologist. From the radiologist's perspective, the goal is very simple: to obtain a sufficient amount of material through the needle to allow the pathologist to make a diagnosis with a minimum of complications to the patient. Similarly, the goal of the pathologist is to determine quickly and accurately whether the specimen procured is adequate, thereby avoiding having the radiologist obtain additional samples that would lengthen the procedure and increase the risk of complications. The pathologist must then determine how the specimen should be analyzed to maximize yield. Special techniques in TNB are used with a view toward these goals. This article defines three distinct aspects of TNB and for each describes various techniques that we believe are helpful in enhancing them. These include placement of the needle tip within the nodule, cytologic techniques for maximizing specimen yield for immediate review, and strategies for pathologic analysis and minimizing complications.