Hypereosinophilic syndrome (HES) is a heterogeneous group of disorders characterized by persistent peripheral hypereosinophilia and eosinophilia-mediated tissue damage. Hypereosinophilic syndrome can have life-threatening effects on multiple organ systems but may initially, or in some cases solely, present with skin lesions. The clinical presentation of HES in the skin represents a diagnostic challenge for the dermatologist, because cutaneous manifestations are highly variable and may be mistaken for several dermatologic conditions. Once peripheral and tissue eosinophilia is diagnosed, the differential diagnosis is quite broad, spanning hematoproliferative disorders, infectious diseases, drug reactions, and many others. Workup and management may also present a challenge, because the prospect for organ system involvement in those with apparent skin-limited disease is unclear. This article provides a dermatology-centered approach to HES and provides a reference for the differential diagnosis, workup, and management of this complex disorder.