Background: Skin prick test (SPT) has been identified as the gold standard method to diagnose IgE mediated hypersensitivities; it is accurate, easy and cheap. However, SPT has some important limitations, so in vitro serum specific serum IgE (sSIgE) detection can be a good alternative. The diagnostic yield of sSIgE testing usually depends on the specific allergen. Objective: This study compares between SPT and sSIgE for diagnosis of allergy. Methodology: 61 allergic patients enrolled from Zagazig University Allergy and Immunology Unit, tested by SPT for the common allergens. Serum total IgE and specific IgE levels were measured and compared to SPT results. Results: The over- all sensitivities of sSIgE were excellent (75-100%) for most of allergens tested. PPV was excellent with some allergens (pollens, cockroaches, mites) and poor with others (cat hair). Sensitivity of mites sSIgE was excellent with PPV approaching 90%, specificiy was only 13%. However, the NPV was 100%. Significant level of agreement and correlation between the results of SPT and sSIgE for cockroaches and molds was reported. Positive correlation between the total levels of serum IgE and the diameter of wheal and flare of the SPT for mites, pollens and cockroaches was found. Conclusion: The sensitivities of sSIgE were excellent for most of allergens tested. Specificity of sSIgE varies between individual allergens. Serum specific IgE testing may be a good alternative to skin prick test if the latter could not be carried out.