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Trans-esophageal endoscopic ultrasound with fine-needle aspiration (EUS-FNA) is widely used to assess mediastinal masses. Common complications are self-limiting bleeding or pain, but occasionally, more serious accidents have been reported. A 54-year-old woman with a huge mass located in the left middle mediastinum presented 2 days after an EUS-FNA with dyspnea and chest pain. Computed tomography scan showed a massive left pleural effusion. A chest tube was inserted revealing a chylothorax (1800 ml). Over the following days, the pleural effusion did not diminish, requiring a left mini-thoracotomy. Intraoperative findings showed a pedunculated mass arising from the upper lobe. A wedge resection and a ligation of a large lymphatic vessel were performed. Postoperative course was regular. Histology showed a solitary fibrous tumor of the pleura. To our knowledge, the case we describe is the first reported chylothorax after EUS-FNA. Despite the demonstrated safety, particular care is mandatory in case of large, vascular, and heterogeneous masses.