Patients with Marfan syndrome present anatomic variations that may increase the risk of a difficult airway. Moreover, they can present large aortic aneurysms, which may cause extrinsic airway compression. Therefore, difficult ventilation during general anesthesia poses a challenge in that the anesthesiologist has to promptly make a crucial differential diagnosis. Multidisciplinary preoperative assessment and planning of the airway and ventilation management are of utmost importance in such uncommon and highly complex clinical cases. Fiberoptic bronchoscopy is probably a really useful tool in order to assess the severity and extent of the airway compression, both preoperatively and intraoperatively. We present a clinical case where difficult ventilation occurred immediately after the induction of general anesthesia.