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Allergy consists of a group of heterogeneous diseases with different underlying mechanisms. However, common allergies including eczema, hay fever, and allergic asthma, characterized by immediate hypersensitivity reactions, are mediated by IgE, which is produced and regulated by the B cells as well as T helper type 2 (Th2) and type 17 (Th17) cells (1–3). Allergic symptoms result from cross-linking of IgE to an allergen on the surface of mast cells, leading to the release of granules including histamine and other inflammatory substances. Two broad classes of IgE participate in the allergic response, allergen-specific IgE, which recognizes specific components of an allergen, and total IgE, which recognizes these components and, in addition, includes antibodies of unknown specificity and function (4). Levels of allergen-specific IgE are used, together with allergic symptoms, to diagnose allergies. However, there are allergies, such as contact allergies, that do not involve IgE (5), and conversely, elevated levels of either allergen-specific or total IgE are not necessarily associated with allergic symptoms (6,7). Many observational studies have been conducted to determine whether having a history of allergy is associated with a reduced risk of cancer (8,9). Findings from most of these studies are conflicting, with varying results both within and among cancer sites. In contrast, the inverse association between self-reported allergy and glioma has been consistently observed in case–control studies (10–12). In addition, there are two recent nested case–control studies (13,14), in which prediagnostic IgE concentration was used as a biomarker of allergy. In the first study, Schlehofer et al. (13) found an association between those testing positive for respiratory allergen-specific IgE (>0.35 kUA/L) and decreased risk of glioma compared with those testing negative (≤0.35 kUA/L) (odds ratio [OR] = 0.73, 95% confidence interval [CI] = 0.51 to 1.06). In contrast, Calboli et al. (14) found no association between prediagnostic respiratory allergen-specific IgE levels and risk of glioma. However, they reported an association between borderline elevated total IgE levels (25–100 kU/L) and decreased risk of glioma compared with normal levels ( 100 kU/L) compared with normal levels (14). Glioma consists of morphologically heterogeneous tumors reflecting germline genetic variation and possibly differences in etiology (15), and the most common glioma subtype is glioblastoma. Schlehofer et al. (13) found that the association between testing positive for respiratory allergen-specific IgE and high-grade (grade 3 [anaplastic astrocytoma] and grade 4 [glioblastoma]) glioma (a category that consists of both anaplastic astrocytoma and glioblastoma) was stronger than the association between testing positive for allergen-specific IgE and all grades of glioma combined. Although Calboli et al. (14) reported that stratifying on glioblastoma did not substantially alter their results, their sample was small (n = 103 glioblastoma case subjects), making this finding difficult to interpret. In this study, we aimed to further determine the degree to which respiratory allergen-specific or total IgE levels are associated with the risk of glioma or glioblastoma. We conducted a nested case–control study using prospectively collected stored serum samples from the Janus Serum Bank (Oslo, Norway).