Background : The cross- reactive carbohydrate determinants (CCD) are protein- linked carbohydrate structures responsible for IgE cross- reactivity towards a wide range of allergens from plants and inver-tebrates. Up to know specific IgE to CCD has never been reported to cause any clinical symptom. To define the prevalence of anti- CCD IgE in a large population and report their impact on IgE detection by means of a multiplex in vitro testing system bearing allergenic molecules and extracts. Method : Sera from 12 545 patients were tested by means of FABER test, a nanobead- based multiplex IVD test for specific IgE detection bearing 122 molecular allergens and 122 allergenic extracts, all cou-pled to chemically activated nanopar ticles. Four markers of CCD- IgE reactivity are available for the purpose: Ana c 2, Arm r HRP, Hom s LF, Sola t 1. Results : Out of 12545 tested sera 9429 resulted to be IgE positive to at least one of the 244 allergenic preparations. Among them 2107 patients (22%; M/F 1.25) recognized at least one of the four CCD markers. The analysis by age showed up a maximum prevalence (34%) within the first decade, decreasing by age down to a minimum preva-lence of 8% in the in the over 80 and 90 years old. Within the 2107 patients the most recognized CCD marker was Arm r HRP (73%), fol-lowed by Hom s LF (54%), Ana c 2 (53%), Sola t 1 (37%). The analysis by gender showed an equal prevalence (53%) for Ana c 2 while for the other 3 CCD markers the prevalence was always higher in males. Nevertheless, the analysis of the 858 monosensitized patients (422 M and 436F) showed for Ana c 2 a higher prevalence (27%) in Females vs a lower (14%) in Males. In case of CCD- IgE detection a broad plant- derived extracts recognition was recorded, and the parallel use of other molecular markers helped the diagnostic interpretation of the test. Conclusion : The presence of IgE directed against CCD can be de-tected in 1 of 5 allergic subjects. A careful examination using CCD markers is utmost importance for the correct interpretation of the lab test results. Due to the quite high prevalence of CCD- IgE, one or more CCD markers should be used in singleplex systems when esting plant- derived extracts or molecules. Further studies are re-quired to understand why CCD markers are recognized by some pa-tients only and the possible role they play in the allergic diseases. Further studies are required to understand why CCD markers are recognized only by some patients and the possible role they play in the allergic diseases.