A healthy 23-year-old female developed generalized pruritus over a year that began on her feet and gradually progressed to involve more than 50% of her entire body surface area. Punch skin biopsies were inconclusive, whereas a two-view chest x-ray was suspicious for lymphadenopathy. A chest computed tomography scan with contrast identified an anterior mediastinal mass which was biopsied and diagnosed as a nodular sclerosis type of Hodgkin's lymphoma. Subsequently, appropriate therapy was initiated resulting in complete resolution of the patient's chronic itch. This case underscores the clinical significance of a comprehensive systemic evaluation in chronic pruritus of unclear etiology.