AERD/Samter’s Triad is characterized by allergic-like reactions to aspirin and other nonsteroidal anti-inflammatory drugs, although it is not a true immunoglobulin E (IgE)–mediated allergy. Allergies to other substances, including pollens, animals, and other environmental agents can exist in patients with AERD, but are not characteristic of the disease. Interestingly, we have found a subgroup of patients with AERD who do not have any true allergies, yet have abnormally elevated serum total IgE, an antibody usually related to allergic diseases. Of 82 patients with AERD who were included in this analysis, 22 did not have any allergies identified to either foods or environmental substances, and of those, six had abnormally elevated levels of serum total IgE. This subgroup did not differ from the overall population of patients with AERD in terms of blood eosinophil count. While further research is necessary to uncover both the cause and the mechanism behind this phenomenon, its existence may be helpful in diagnosing AERD.