Eosinophilic granuloma is rarely reported within lymph nodes. Furthermore, it is even more rarely reported in the setting of human immunodeficiency virus (HIV) infection. No definitive etiologic association exists between Langerhans cell histiocytosis (LCH) and HIV. However, their potential relationship underscores the significance of cytokines and their influence on biological niches required for Langerhans development and homeostasis.