Mastocytosis is a spectrum of disorders characterized by an aberrant proliferation of tissue mast cells. Although this disease process often affects the skin, it may involve multiple organs. The clinical disorder varies according to patient age, the clinical manifestations demonstrated, and the extent of the mast cell proliferative process. A myriad of clinical symptoms occur, and these may be localized to the organ system involved or may be systemic, depending on whether there is local or generalized mast cell mediator release. Diagnosis includes the demonstration of increased tissue mast cells in involved organs as well as increased levels of biochemical mediators. Patients with cutaneous involvement only have the best prognosis. Treatment is directed toward stabilizing mast cell mediator release and blocking the effects of those mediators generated.