Our knowledge on the variability of FCER1A gene encoding for alpha-subunit of the high-affinity immunoglobulin E receptor (FcepsilonRI) that plays a central role in the pathogenesis of allergy and related disorders, has been recently much extended. Last findings from FCER1A mutational screening and genetic association studies, followed by functional analyses of the polymorphisms, are briefly summarized in this mini-review. The association between FCER1A gene variants and total serum IgE levels seems especially interesting and, supported by functional analyses of polymorphisms, may provide a rationale for pharmacogenetic studies on anti-IgE therapy that indirectly suppresses FcepsilonRI expression.