AbstractBackgroundPollen allergy poses a significant health and economic burden in Europe. Disease patterns are relatively homogeneous within Central and Northern European countries. However, no study broadly assessed the features of seasonal allergic rhinitis (SAR) across different Southern European countries with a standardized approach.ObjectiveTo describe sensitization profiles and clinical phenotypes of pollen allergic patients in nine Southern European cities with a uniform methodological approach.MethodsWithin the @IT.2020 multicenter observational study, pediatric and adult patients suffering from SAR were recruited in nine urban study centers located in seven countries. Clinical questionnaires, skin prick tests (SPT) and specific IgE (sIgE) tests with a customized multiplex assay (Euroimmun Labordiagnostika, Lübeck, Germany) were performed.ResultsThree hundred forty‐eight children (mean age 13.1 years, SD: 2.4 years) and 467 adults (mean age 35.7 years SD: 10.0 years) with a predominantly moderate to severe, persistent phenotype of SAR were recruited. Grass pollen major allergenic molecules (Phl p 1 and/or Phl p 5) ranged among the top three sensitizers in all study centers. Sensitization profiles were very heterogeneous, considering that patients in Rome were highly poly‐sensitized (sIgE to 3.8 major allergenic molecules per patient), while mono‐sensitization was prominent and heterogeneous in other cities, such as Marseille (sIgE to Cup a 1: n = 55/80, 68.8%) and Messina (sIgE to Par j 2: n = 47/82, 57.3%). Co‐sensitization to perennial allergens, as well as allergic comorbidities also broadly varied between study centers.ConclusionsIn Southern European countries, pollen allergy is heterogeneous in terms of sensitization profiles and clinical manifestations. Despite the complexity, a unique molecular, multiplex, and customized in‐vitro IgE test detected relevant sensitization in all study centers. Nevertheless, this geographical diversity in pollen allergic patients imposes localized clinical guidelines and study protocols for clinical trials of SAR in this climatically complex region.