Recently introduced "second-generation" techniques for specific IgE measurement have produced some analytical improvement, offering better clinical sensitivity than previous techniques. The aims of our study were to compare the analytical and clinical performances of four second-generation techniques for allergen-specific IgE measurement in serum and to ascertain whether the new system for reporting quantitative results contributes to greater clinical agreement between findings using the techniques considered. Allergen-specific IgE was measured using the CAP System, CARLA, ENEA, and AlaSTAT, and the findings were compared. A significant disagreement was found between CAP and ENEA for all allergens and between CAP and CARLA for D1 and G5. However, the clinical discrepancies were reduced by selecting method-specific thresholds using ROC analysis. Second-generation techniques enable us to obtain better standardization of results; however, the identification of a specific threshold appears to be a prerequisite for the appropriate clinical interpretation of the test findings.