Chronic idiopathic urticaria (CIU) is diagnosed in patients when urticarial eruptions recur for more than 6 weeks, and no specific cause is determined. Given that urticaria resembles the lesions induced by injection of histamine or allergen into the skin, a role for mast cells or basophils has been proposed in the generation of localized urticarial lesions. However, currently, the exact mechanisms governing regional mast cell or basophil activation are unknown. In the past decade, there has been mounting interest in viewing CIU as an autoimmune disease, given the presence of circulating autoantibodies to IgE or the alpha subunit of the high-affinity IgE receptor (FceRI) in a subset of patients. In this review, we propose that in addition to autoantibodies, specific differences in the expression of FceRI-signaling molecules in the basophils or mast cells of CIU patients may contribute to the generation of urticarial eruptions.