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Acquired angioedema with low C1-inhibitor (AAE-C1-INH) is a rare disorder characterized by an acquired deficiency in the C1 esterase inhibitor (C1-INH). This case report describes a 79-year-old patient presenting to the emergency department for painless swelling of his scrotum, penile shaft, and left lower and upper extremities with lab values consistent with acquired angioedema without identifiable lymphoreticular or rheumatic disorder on history, exam, or total body PET scan. Proper diagnosis of AAE-C1-INH is essential to prevent life-threatening airway compromise, ensure proper therapy, and exclude lymphoreticular disorders as the etiology of AAE-C1-INH.