Mast cells (MCs) perform multiple functions thought to underlie different manifestations of allergies. Various aspects of antigens (Ags) and their interactions with immunoglobulin E (IgE) cause diverse responses in MCs. FcεRI, a high-affinity IgE receptor, deciphers the Ag–IgE interaction and drives allergic responses. FcεRI clustering is essential for signal transduction and, therefore, determines the quality of MC responses. Ag properties precisely regulate FcεRI dynamics, which consequently initiates differential outcomes by switching the intracellular-signaling pathway, suggesting that Ag properties can control MC responses, both qualitatively and quantitatively. Thus, the therapeutic benefits of FcεRI-targeting strategies have long been examined. Disrupting IgE–FcεRI interactions is a potential therapeutic strategy because the binding affinity between IgE and FcεRI is extremely high. Specifically, FcεRI desensitization, due to internalization, is also a potential therapeutic target that is involved in the mechanisms of allergen-specific immunotherapy. Several recent findings have suggested that silent internalization is strongly associated with FcεRI dynamics. A comprehensive understanding of the role of FcεRI may lead to the development of novel therapies for allergies. Here, we review the qualitatively diverse responses of MCs that impact the attenuation/development of allergies with a focus on the role of FcεRI toward Ag exposure.