Diagnosis of indeterminate mediastinal masses and staging of lung cancer poses a significant challenge. Options for tissue diagnoses include computed tomography (CT)-guided percutaneous biopsy, transbronchial fine-needle aspiration, mediastinoscopy/mediastinotomy or thoracoscopy, but these investigations have limitations in terms of tissue yield, safety profile and cost. Trans-esophageal endoscopic ultrasound scanning (EUS) is a new minimal invasive method that provides high resolution imaging of the mediastinum using high frequency ultrasound probes attached to the tip of a flexible endoscope and offers in addition the facility of fine needle aspiration (EUS-FNA) or tru-cut biopsy (TCB) under real-time ultrasound guidance. EUS-FNA allows access to the posterior mediastinum and tissue acquisition under real-time ultrasound guidance through the oesophageal wall. Indications of EUS-FNA in the mediastinum is to obtain a diagnosis from an unknown primary lesion or to sample tissue from mediastinal lymph nodes in order to stage lung cancer or to diagnose other diseases involving lymph nodes of the mediastinum eg. TB, Sarcoidosis, histoplasmosis or metastases from a vide range of cancers. If lymphoma is suspected EUS-TCB of an enlarged mediastinal lymph node is preferred. EUS- FNA is safe, can be done on an outpatient basis, is well tolerated and provides an excellent diagnostic yield with a sensitivity of more than 90% and a specificity of 100%. Compared to CT, PET, mediastinoscopy as well as transbronchial aspiration, EUS-FNA is found to be significant more accurate for staging of non-small cell lung cancer. However, mediastinoscopy is at present still regarded as the gold standard in the region of the anterior mediastinum since EUS can not image this region due to the air-filled trachea. Recently, endobronchial ultrasound guided transbronchial needle aspiration Biopsy (EBUS-TBNA) has been developed and several publications have now documented high diagnostic values with sensitivities of more than 90% in the staging of NSCLC. A recent publication from our group has documented a sensitivity and specificity of 100% when EUS-FNA and EBUS-TBNA is used in combination for staging of the mediastinum. It seems therefore logical to assume that the combination of EUS-FNA and EBUS-TBNA will replace more invasive methods such as mediastinoscopy for diagnosis and staging of lung cancers in the near future.