This review aims to provide an overview of the molecular pathophysiology, focusing on mutations in genes such as those involved in the MAPK and PI3K-AKT signaling pathways and discusses the evolving treatment strategies for histiocytic neoplasms, focusing on conditions, with a particular focus on the four major types: LCH, ECD, RDD, and JXG. This evidence concerns the gene PIK3CA and Langerhans cell histiocytosis.