Tehran University of Medical Sciences Frontiers in Dentistry 2676-296X 22 0 2025 01 18 4462 4462 Shabnam Mashhadi Department of Pathology, Cancer Institute, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran Ata Garajei Department of Head and Neck Surgical Oncology and Reconstructive Surgery, Cancer Institute, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran Pouyan Aminishakibb Department of Pathology, Cancer Institute, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran 2.Oral and Maxillofacial Pathology Department, School of Dentistry, Tehran University of Medical Sciences, Tehran, Iran 2022 05 05 2023 05 23 Rhabdomyosarcoma is a rare soft tissue malignant neoplasm with striated muscle differentiation often found in the head and neck region. In our case a 33-year-old man presented with a bulging mass near his right mandibular second molar tooth, identified as a unilocular destructive lesion on an X-ray. An incisional biopsy confirmed rhabdomyosarcoma, leading to a hemi-mandibulectomy. Histopathologic findings showed spindle and rhabdoid cells with positive immunoreactivity to Desmin, myogenin and myoD1. In conclusion, it is crucial to differentiate rhabdomyosarcoma from other more common intraosseous malignancies, and using Desmin staining as part of the initial immunohistochemical panel can aid in the diagnosis process. https://fid.tums.ac.ir/index.php/fid/article/view/4462