Background <p>DEK::AFF2 fusion–associated nonkeratinizing squamous cell carcinoma is a recently recognized HPV-independent entity characterized by deceptively bland morphology and potential mimicry of benign or inflammatory lesions.</p> Case Presentation <p>A 21-year-old woman presented with recurrent left-sided otorrhea and progressive hearing loss. Imaging demonstrated noncontiguous lesions involving the left middle ear/mastoid compartment and the sinonasal region. Histologically, both lesions showed nonkeratinizing squamous proliferation with focal papillary/inverted architecture, mild to moderate cytologic atypia, and focal stromal invasion. Immunohistochemically, the tumor exhibited diffuse nuclear AFF2 expression, positivity for CK5/6 and p40, wild-type p53 expression, and negative p16 and INSM1. Targeted next-generation sequencing confirmed DEK::AFF2 fusion in both lesions.</p> Conclusion <p>This case expands the anatomic spectrum of DEK::AFF2 fusion–associated nonkeratinizing squamous cell carcinoma by demonstrating noncontiguous middle ear and sinonasal involvement. Recognition of its characteristic morphologic, immunophenotypic, and molecular features is essential to avoid misdiagnosis.</p> Graphical Abstract <p></p>