Autoimmune lymphoproliferative syndrome (ALPS) is a disorder of lymphocyte apoptosis characterized by nonmalignant lymphadenopathy, splenomegaly, immune dysregulation, and autoimmune cytopenias. Langerhans cell histiocytosis (LCH) is a neoplasm of myeloid precursor cells, primarily presenting as bone, soft tissue, lung, skin, and pituitary lesions. The association between the two diagnoses is uncharacterized. Here we describe a patient presenting with fever of unknown origin, cytopenias, and failure to thrive. She was diagnosed with ALPS, then subsequently LCH, within three months. This case highlights the diagnostic and management challenges associated with these two rare diagnoses.