Summary: We describe the case of a thoracoscopic approach to giant lymph node hyperplasia (Castleman's disease) located in the mediastinum. In our patient the initial diagnosis was substernal goiter, but at cervical exploration the mass was found not to be continuous with the thyroid. The mass was easily identified through a lateral thoracoscopic approach and carefully removed. The postoperative course was uneventful, and the patient was discharged home on the fifth postoperative day. Histopathology revealed the features of Castleman's disease, mixed type. The prevalence, location, and pathogenesis of giant lymph node hyperplasia are described, together with the histology and clinical signs. Our report is proposed as the first case of an endoscopic approach to giant lymph node hyperplasia, which could be the best surgical approach for a mediastinal location.