Tehran University of Medical Sciences Journal of Craniomaxillofacial Research 2345-5489 13 3 2026 10 24 385 392 EN Faezeh Khozeimeh Department of Oral Medicine, School of Dentistry, Isfahan University of Medical Sciences, Isfahan, Iran. Mohammad Hosein Amirzade-Iranaq Post Graduate Student, Student Research Committee, Department of Oral Medicine, School of Dentistry, Isfahan University of Medical Sciences, Isfahan, Iran. Elahe Soufian Department of Oral Medicine, School of Dentistry, Isfahan University of Medical Sciences, Isfahan, Iran. Seyed Amirhossein Rahimizadeh Hosseini Post Graduate Student, Department of Oral and Maxillofacial Surgery, School of Dentistry, Isfahan University of Medical Sciences, Isfahan, Iran. Laleh Maleki Dental Research Center, Department of Oral and Maxillofacial Pathology, School of Dentistry, Isfahan University of Medical Sciences, Isfahan, Iran. 2026 06 21 2026 09 24 Isolated plasmacytoma relapse of multiple myeloma (MM) is uncommon and portends a poor prognosis; mandibular involvement is exceptionally rare, and its clinical presentation in the post-autologous stem cell transplantation (ASCT) setting, particularly in patients with prior bisphosphonate exposure, can closely mimic medication-related osteonecrosis of the jaw (MRONJ), creating a critical diagnostic pitfall. A 62-year-old male with MM in sustained remission following ASCT and lenalidomide maintenance presented with a seven-month history of a non-healing extraction socket and progressive exophytic mandibular mass. Prior zoledronic acid therapy led to an initial diagnosis of MRONJ, delaying biopsy. Clinical examination revealed a 4×3 cm firm mass with lingual bone exposure; contrast-enhanced CT demonstrated osteolytic cortical destruction with inferior alveolar canal invasion and indeterminate incidental vertebral lytic foci. Incisional biopsy confirmed sheets of atypical plasma cells with eccentric nuclei and prominent mitotic activity, consistent with plasmacytoma. Comprehensive systemic workup, including bone marrow biopsy and serum protein electrophoresis, confirmed the absence of systemic MM relapse. The patient was treated with external beam radiotherapy (40 Gy in 20 fractions), achieving significant lesion regression. Focal residual bone exposure (<1 cm) attributed to combined bisphosphonate-radiation osteonecrosis was managed conservatively. The patient reported functional recovery and maintained acceptable quality of life at the three-month follow-up, with no evidence of local recurrence or systemic relapse. This case highlights that persistent oral lesions in MM patients must not be reflexively attributed to MRONJ without histopathological verification, especially when lesions fail to resolve following bisphosphonate cessation. Multidisciplinary surveillance at the oncology–dentistry interface is essential to avoid diagnostic delay in this vulnerable population.  Keywords: Multiple myeloma; Plasmacytoma; Mandibular neoplasms; Stem cell transplantation; Case report. https://jcr.tums.ac.ir/index.php/jcr/article/view/680 https://jcr.tums.ac.ir/index.php/jcr/article/download/680/521