Tehran University of Medical Sciences Journal of Craniomaxillofacial Research 2345-5489 12 3 2025 12 07 201 205 Bahareh Fattahi Department of Oral and Maxillofacial Pathology, School of Dentistry, Kashan University of Medical Sciences, Kashan, Iran. Arash Esmaeili Department of Oral and Maxillofacial Surgery, School of Dentistry, Isfahan University of Medical Sciences, Isfahan, Iran. Akram Fallah Department of Oral and Maxillofacial Radiology, School of Dentistry, Isfahan University of Medical Sciences, Isfahan, Iran. Saeedeh Khalesi Department of Oral and Maxillofacial Pathology, School of Dentistry, Isfahan University of Medical Sciences, Isfahan, Iran. 2025 07 11 2025 08 12 Primary neuroendocrine carcinomas (NECs) of the oral cavity represent exceptionally rare malignancies (< 30 reported cases globally), posing significant diagnostic challenges due to histological mimicry of other round cell tumors and nonspecific clinical presentation. This report details a novel case with atypical clinicopathological features and favorable therapeutic outcomes. A 38-year-old male presented with a 3-month history of a right hard palate ulceration. Clinical examination revealed an indurated endophytic lesion. Histopathology and immunohistochemistry confirmed poorly differentiated large cell NEC. Due to unresectable pterygopalatine fossa involvement, chemoradiation was administered. Given the extreme rarity of oral large cell neuroendocrine carcinoma (LCNEC), clinicians must consider this entity even in patients lacking traditional risk factors (e.g., smoking). Its aggressive growth pattern and metastatic propensity necessitate prompt specialist referral for early intervention.  Keywords: Oral pathology; Neuroendocrine carcinoma; Large cell carcinoma. https://jcr.tums.ac.ir/index.php/jcr/article/view/550 https://jcr.tums.ac.ir/index.php/jcr/article/download/550/461