Endoscopic ultrasound-guided fine-needle aspiration (EUS FNA) is an accurate and versatile technique in the diagnosis of gastrointestinal tract lesions as well as other organ sites. EUS FNA is performed ideally with cytopathologic adequacy evaluation, and diagnosis at the time of tissue procurement. In this article, we review the most relevant issues in the process of EUS FNA-based diagnostics. Specifically, we describe the technical aspects of specimen collection, processing, and appropriate selection of ancillary studies. We also illustrate the most commonly encountered diagnostic pitfalls, and methods for their avoidance. Lastly, we discuss quality management, which emphasizes the communication between the endoscopist and the pathologist. © 2007 AGA Institute.