Endoscopic ultrasound (EUS) is an indispensable tool for tissue acquisition in patients with gastrointestinal tumors. While fine-needle aspiration (FNA) has been routinely carried out for establishing tissue diagnosis, the emerging concept of tailoring chemotherapeutic agents based on molecular markers has increased the demand for core tissue procurement by means of EUS-guided fine-needle biopsy (EUS-FNB). In addition, FNB may offset the limitations of FNA wherein the diagnostic sensitivity is incumbent on the availability of an onsite cytopathologist. Given the increasing number of procedures being done, developing a unit-specific algorithmic approach for needle selection is important to improve the procedural efficiency and utilization of resources. Finally, the best outcomes can be attained only by practicing evidence-based techniques, procuring adequate quantity of sample for ancillary studies and processing the specimens appropriately.