Although there is no doubt about the influence of the genetic background in the onset of the allergic diseases, Epigenome-Wide Association Studies are needed to elucidate the possible relationship between allergic diseases and epigenomic dysregulation. In this study we aimed to analyze the epigenetic patterns, in terms of DNA methylation, of three well-characterized populations of house dust mite allergic subjects, aspirin-intolerant asthmatics and controls. As a first, genome-wide phase, we used the HELP assay to study the methylation patterns in CD19 (+) B lymphocytes in these populations, and found that there are reproducible epigenetic differences at limited numbers of loci distinguishing the groups, corroborated by bisulphite MassArray in a second validation phase of an expanded 40 subject group. These validated epigenetic changes occur at loci characterized as important for the immune response. One such locus is a new candidate gene, CYP26A1, which shows differential methylation patterns and expression levels between groups. Our results suggest that epigenomic dysregulation may contribute to the susceptibility to allergic diseases, showing for the first time differences in DNA methylation between allergic and non-allergic healthy subjects, both globally and at specific loci. These observations indicate that the epigenome may offer new pathophysiological insights and therapeutic targets in atopic diseases.