Chronic urticaria (CU) is defined as recurrent, transitory, pruritic-raised wheals present on most days of the week for> 6 weeks1. The pathogenesis of CU is unknown; but it is thought to be the result of autoimmunity, at least in some patients. Evidence supporting this comes from assays suggesting the presence of functional autoantibodies. IgG autoantibodies to IgE or to the high-affinity IgE receptor (FcεRI) have been directly detected in~ 40-50% of CU patients. 2 While of interest, identifying these antibodies is laborious and not fully validated, therefore, numerous surrogate assays have been developed. A positive autologous serum skin test (ASST) can be identified in 30-67% of CU patients3 and is an indirect reflection of autoantibodies. However, the ASST is positive in 37% of non-CU patients3, making it of less certain clinical relevance. Alternatively, the sera of 40-50% of CU patients can induce the release of histamine from the basophils of healthy subjects (basophil histamine-releasing assay, HRA). 4 Limitations to this test are based on inter-laboratory reproducibility and variation in healthy basophil donor characteristics; 2 and as with the ASST, the HRA lacks diagnostic specificity for CU. More recently, flow cytometry has been used to evaluate the ability of CU patients’ serum to activate donor basophils as determined by the upregulation of CD203c (ectonucleotide pyrophosphatase/phosphodiesterase) 5 In the validation studies for this assay, the upregulation of CD203c surface expression was evaluated on basophils obtained from a healthy atopic donor after exposure for 10 minutes to serum obtained from 32 CU patients and 11 healthy controls.(see Yasnowsky et al. 5 for more detailed description). The data are expressed as the percent of basophils expressing more CD203c than 99% of basophils incubated with buffer only. A result≥ 5% is highly specific for CU as this result was never seen using serum obtained from healthy controls5. Serum factors driving increased CD203c-expression in this assay are unknown and as with the HRA are assumed to reflect autoantibodies, however this has never been determined. Furthermore,