The Pemberton maneuver is a tool that may be utilized during the physical examination to demonstrate the presence of latent pressure in the thoracic inlet [1]. The maneuver is achieved by having the patient elevate both arms until they touch the sides of the face. A positive sign is marked by the presence of facial congestion and cyanosis, as well as respiratory distress after approximately one minute [2]. The sign is most commonly present in patients with substernal goiters where the goiter "corks off" the thoracic inlet [3]. We describe a 67-year-old Caucasian male with a positive Pemberton's sign due to compression of the thoracic inlet by enlarged mediastinal nodes. The sign was amplified by the presence of a restrictive cardiomyopathy and constrictive pericarditis due to amyloidosis. We propose that a positive Pemberton's sign should not be used exclusively to evaluate the probability of a substernal goiter, but rather to assess the potential for vascular compression due to pathological changes in the anatomical environment of the thoracic inlet.