Mastocytosis is a disease characterized by an abnormal increase in mast cells. Manifestations of the disease are provoked in large part by the resultant increase in mast cell-derived mediators, which have a variety of local and systemic effects. Mastocytosis is variable in respect to the organ systems involved, clinical manifestations, and association with hematologic diseases. This has suggested the need for an improved classification scheme to allow assessment of prognosis and therapy. The heterogeneity of the disease patterns in mastocytosis strongly suggests that more than one biologic lesion may occur in the developmental sequence that leads to placement of mature mast cells in tissues.