Objective:To investigate the clinicopathological features and differential diagnosis of primary pulmonary hyalinizing clear cell carcinoma (HCCC), as well as its diagnostic pitfalls in assessing biopsy specimens.Methods:Five cases of primary pulmonary HCCC diagnosed in the Department of Pathology, Shanghai Chest Hospital, Shanghai, China from August 2019 to December 2023 were collected. The clinicopathological characteristics, immunohistochemistry, and the EWSR1 gene related translocation and fusion were summarized, and relevant literature was reviewed.Results:Among the five cases of HCCC, two were males and three were females, with ages ranging 36-74 years. The tumors were located in the lumen of the bronchus or trachea and showed an exophytic polypoid growth pattern. The maximum diameter of the tumors ranged from 1.3 to 5.0 cm. Histologically, the tumor cells showed transparent cytoplasm and slight cellular atypia, with medium-sized round cells arranged in cords, nests, and trabecula. Small nucleoli were noted, while mitotic figures were rare. The interstitial bands of the tumor in various thickness were anastomosed with hyalining and sclerosing fibrous tissues. All the tumor cells were positive for CKpan, CK7, p40, p63 and CK5/6, but negative for S-100, SMA, Calponin, TTF1 and Napsin A; Ki-67 proliferation index was less than 10% (1%-10%). FISH testing showed EWSR1 gene translocation in all cases, three of which were confirmed by next generation sequencing to have EWSR1::ATF1 gene fusion.Conclusions:Biopsy specimens of primary HCCC in the lungs are prone to misdiagnosis due to the expression of squamous cell carcinoma biomarkers, which poses a unique challenge. A complete understanding of the morphological characteristics of primary pulmonary HCCC, combined with immunohistochemistry and molecular testing, is helpful to reach accurate diagnosis.