Background: Atopic dermatitis (AD) is a chronic skin condition impacting quality of life. Allergen recognition via specific IgE triggers immune responses and allergy symptoms. Cross-reactivity may induce auto-IgE responses and worsen AD. We aimed to analyze molecular mimicry between human AQP3 and Aspergillus fumigatus aquaporin, a potential allergen source. Methods: In silico analysis compared human (AQP3) and A. fumigatus aquaporin sequences with 25 aquaporins from allergenic sources. Sequences were obtained from UniProt and NCBI. Phylogenetic relationships and homology-based modeling were performed, with ElliPro predicting conserved antigenic regions on 3D structures. Results: Global identity among aquaporins was 32.6%, but one antigenic site exhibited 71.4% local conservation. Five monophyletic clades (A to E) were formed. Group B showed the highest identity (95%), including 6 mammalian aquaporins, including AQP3. A. fumigatus aquaporin shared the highest identity with Malassezia sympodialis (35%). Both human and A. fumigatus aquaporins featured three linear and three discontinuous epitopes, with a root mean square deviation (RMSD) of 1.006. Conclusion: Possible linear and conformational epitopes on AQP3 were identified. High identity in one antigenic region suggests molecular mimicry between human and A. fumigatus aquaporins, potentially leading to autoreactivity and cross-reactivity. Further in vitro and in vivo studies are needed to confirm these findings.