Mast cells are involved in many immune reactions and diseases through 1) the expressions of several receptors, 2) productions of various mediators such as histamine, cytokines, and chemokines, 3) direct interactions with immune cells. Besides allergic diseases, mast cells have been also assumed to be involved in autoimmune diseases such as bullous pemphigoid, rheumatoid arthritis, and multiple sclerosis. Moreover, several studies reported the involvement of mast cells in collagen disease. In this article, we review recent findings about the role of mast cells especially in systemic lupus erythematosus and systemic sclerosis. In these diseases, mast cells seem to be involved in local inflammation and tissue damage partially in the targeted organ rather than the development of autoimmunity including production of autoantibodies.