Histiocyte disorders are characterized by single or multi-organ infiltration of neoplastic myeloid-derived cells with diverse macrophage and dendritic cell phenotypes with an associated accumulation of inflammatory cells. These inflammatory myeloid neoplastic disorders, affecting both adults and children, are rare and heterogenous with over 100 subtypes described. The four most common histiocyte neoplasms are Langerhans cell histiocytosis, Erdheim-Chester disease, Rosai-Dorfman disease and juvenile xanthogranuloma. The identification of shared ERK activation and somatic mutations in MAPK pathways genes has resulted in better understanding of the pathophysiology of these previously clinically and morphologically linked disorders and has resulted in improved diagnostic tests and expanded treatment options for patients. Dr. Carl Allen will discuss the landscape of mutations found in histiocyte neoplasms. Dr. Eli Diamond will discuss targeted therapies for histiocyte disorders.