EUS guided tissue acquisition has evolved over time in terms of techniques and accessories. In the last decade, fine needle biopsy (FNB) with 19G FNA needle or dedicated FNB needles has been increasingly used in clinical practice. Multiple factors may affect the diagnostic yield of EUS guided tissue acquisition. This lecture aims to review the current data on how techniques of tissue acquisition, needle size and design, lesion type and specimen handling, EUS technology, as well as operator training and experience can impact the quality of EUS guided tissue acquisition.