Nasopharyngeal tonsil (adenoid) hypertrophy (AH) is a common childhood pathology, which causes the obstruction of upper airways. AH is one of the major causes of adenoidectomy in this age group. Several studies report a higher incidence of AH among children with allergies, but underlying molecular mechanisms are still unclear. Adenoids are able of producing proinflammatory and antimicrobial molecules, which influence the immune response. microRNAs (miRNAs) of the adenoid tissues have a distinct expression pattern in allergic patients. miRNAs are small non-coding RNA that bind a target mRNA, regulating gene expression. Extracellular vesicles (EVs) released by tonsil-derived mesenchymal stem cells have regulatory effects on mast cell activation under inflammation. EVs are nano-size membrane vesicles released in physiological and pathological conditions. EVs carry proteins, metabolites, lipids, and nucleic acids, including miRNAs. miRNAs shuttled by EVs are considered potential disease biomarkers. Our study aims to identify a signature of miRNAs selectively packaged in EVs released by adenoid-derived peripheral blood mononuclear cells (aPBMCs). The preliminary data carried out on four pediatric patients were evaluated for miRNA detection in aPBMCs and EVs. The results indicate a selective packaging of miR-21 in EVs isolated by aPBMCs recovered by surgical samples of children with AH. The presence of miRNAs in EVs has never been described in children in secondary lymphoid organs, such as adenoids, constitutively exposed to environmental antigens and allergens. This study can lay the foundation to further investigate miRNA involvement in immune responses, including allergies, of children with AH