Diagnosing unclear lymph node (LN) enlargements in the mediastinum and abdomen is the most important indication of endoscopic ultrasound (EUS)-fine needle aspiration (FNA) after the diagnosis and treatment of pancreatic diseases. Investigating LNs in these areas can happen in different clinical settings. Mostly, it is the first modality in general LN diseases without any peripheral LN enlargements. On the other hand, it can be the question of LN involvement in a known or suspected primary tumor. Due to EUS-FNA cytology, those questions can be answered highly, accurately. However, a primary discrimination of LNs might be helpful to increase the diagnostic value of the FNA cytology, especially in cases with multiple LN enlargements and hard to reach enlarged LNs for example by vessel interposition. Because of the unreliability of B-mode criteria, further diagnostic improvements such as elastography and contrast-enhanced EUS are investigated to increase the accuracy of the initial diagnosis.