Mast cell disorders can be separated into those involving proliferation and activation. Mastocytosis is a clonal proliferative disorder of the mast cell and its progenitor. Reactive mast cell hyperplasia can be seen in a number of inflammatory and neoplastic conditions. Mast cell activation disorders (MCADs) include a broad range of conditions stemming from primary (mastocytosis/monoclonal MCAS), secondary (IgE and non–IgE-mediated mast cell activation due to allergic and nonallergic inflammatory and neoplastic diseases), and idiopathic origins. MCAS is a subgroup of MCADs usually presenting with severe episodic symptoms, which may be similar to anaphylaxis (see text for explanation). There may be overlap in patients with mastocytosis presenting with recurrent anaphylaxis symptoms or in patients with monoclonal MCAS.