Mast cells are bone marrow-derived leukocytes that are released into the circulation as immature cells, which migrate to peripheral tissues where they terminally differentiate. They are found primarily in tissues that interact with the external environment including the skin, lung, and gastrointestinal tract. Upon activation induced by IgE-Fc epsilon RI receptor cross-linking, mast cells release mediators such as histamine, heparin, prostaglandin D2, cysteinyl leukotrienes, chymase, tryptase, and cytokines that have a variety of functions including smooth muscle contraction, increased vascular permeability, mucus production, and immune cell recruitment. Although mast cells are involved in defending the host against pathogens and promoting wound healing, their activity has also been associated with severe allergic reactions, anaphylaxis, and several autoimmune diseases. Flow cytometry can be used to identify mast cells based on their high level expression of CD117/c-kit with variable side scatter, along with expression of IL-3 R alpha/CD123 and Fc epsilon RI. Additionally, mast cells express ENPP-3/CD203c, and CD200 R3 in mice, as well as, the transcription factor, MITF, and they lack expression of MHC class II. Like basophils, mast cells also display upregulated expression of ENPP-3/CD203c and CD63 following activation.