Mastocytosis is a disease characterized by an abnormal proliferation of tissue mast cells. The events primarily responsible for mast cell proliferation in mastocytosis are largely unknown, but a derangement of the network involving c-kit receptor and its natural ligand (stem cell factor, which promotes mast cell growth and differentiation in man) is likely to have a primary role in this disease. Mastocytosis comprises a wide spectrum of clinical conditions determined by the degree of mast cell proliferation, the organ systems involved, the age at onset and the association with hematologic diseases. Mastocytosis can occur in a pediatric or an adult form. In both groups of patients, the disease may be limited to the skin (cutaneous mastocytosis) or be systemic, involving predominantly the bone marrow and the gastrointestinal tract. The symptoms in patients with mastocytosis are generally related to the increased release of mast-cell-derived mediators, such as histamine, prostaglandin D2, peptide leukotrienes, platelet-activating factor, heparin and proteolytic enzymes. The measurement of these chemical mediators (histamine, tryptase and prostaglandin D2 and their metabolites) in body fluids is useful for the diagnosis and the laboratory evaluation of patients with systemic mastocytosis. As little is known about the pathogenesis of the different forms of mastocytosis, the treatment of the majority of these patients is largely symptomatic.