To study clinicopathological features and differential diagnosis of hyalinizing clear cell carcinoma in the head and neck.A retrospective analysis was performed patients with hyalinizing clear cell carcinoma in the head and neck, who underwent surgical resection in Beijing Tongren Hospital affiliated to Capital Medical University from January 2014 to May 2024. The clinical features of HCCC were analyzed by computed tomography and magnetic resonance imaging. Tumor sections were further characterized using hematoxylin and eosin staining, immunohistochemistry, and fluorescence in situ hybridization.There were 4 male and 5 female cases in 9 patients. The age range was 28-84 years-old, the middle age was 60 years-old. 9 patients, 5 in the nasopharynx, 2 in the base of the tongue, and 2 in the oropharynx. At the cellular level, the HCCC tumors were composed of transparent and eosinophilic cells (in various ratios), which were typically arranged into nests, cords, and trabeculae, and embedded in a glassy hyaline substance. Immunohistochemical evaluation showed positivity for CK7, P63, P40, CK5/6, and negativity for S100, SMA, GFAP, and calponin. Fluorescence in situ hybridization revealed EWSR1 rearrangement in all the nine patients evaluated.Hyalinizing clear cell carcinoma is a rare low-grade salivary gland carcinoma that mostly occurs in the minor salivary glands. They had an indolent disease course, with few metastases. Our study shows that the above combination of analytical techniques can be used to accurately characterize and diagnose HCCC.Level 1.Copyright © 2025 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier España S.L.U. All rights reserved.