The histiocytoses show variation in clinical and pathologic features, but the molecular alterations that drive the neoplastic process typically converge on common signaling pathways. The same pathway is targeted in primary and secondary H/DC sarcomas, which typically show more marked cytologic atypia. The presence of specific inhibitors that can target components of the pathway has led to advances in clinical management and improved prognosis in neoplasms of the histiocytic and dendritic cell lineages. The figure has been adapted from Figure 1 in the article by Kemps et al that begins on page 256.