Tehran University of Medical Sciences Journal of Craniomaxillofacial Research 2345-5489 13 3 2026 10 24 381 384 Maryam Tahmasebinasab Department of Oral and Maxillofacial Medicine, School of Dentistry, Tehran University of Medical Sciences, Tehran, Iran. Maryam Koopaie Department of Oral and Maxillofacial Medicine, School of Dentistry, Tehran University of Medical Sciences, Tehran, Iran. 2026 01 02 2026 09 17 Multiple primary malignancies (MPMNs) pose a diagnostic challenge, particularly when a second primary tumor is mistaken for metastasis or a benign lesion related to a known malignancy. This case report highlights the clinical consequences of delayed diagnosis in a patient who developed a second primary squamous cell carcinoma (SCC) of the tongue in the setting of colon adenocarcinoma. A 74-year-old female with a history of colon adenocarcinoma presented with a persistent ulcerative lesion on the left lateral border of the tongue. The lesion was initially managed with topical corticosteroids under the presumptive diagnosis of aphthous ulceration or localized inflammation. Over seven months, the lesion progressively worsened. Incisional biopsy eventually revealed poorly differentiated squamous cell carcinoma. Subsequent PET/CT imaging demonstrated ipsilateral cervical lymph node involvement, consistent with advanced disease. Owing to progression of the malignancy and the patient’s deteriorating systemic condition, definitive surgical treatment could not be performed, and the patient subsequently died. This case demonstrates the critical risk of diagnostic overshadowing and emphasizes the necessity of a strict clinical protocol: any persistent or non-healing oral mucosal ulceration exceeding 2 weeks in oncology patients must mandate an immediate diagnostic biopsy rather than prolonged empirical treatment.  Keywords: Multiple primary malignancies; Squamous cell carcinoma; Tongue; Oral cancer; Delayed diagnosis; Colon adenocarcinoma. https://jcr.tums.ac.ir/index.php/jcr/article/view/613 https://jcr.tums.ac.ir/index.php/jcr/article/download/613/520