Aim: The purpose of this report is to present a case of squamous cell carcinoma (SCC) arising from a mandibular residual cyst. Background: Although rare, SCC may arise in the epithelial lining of odontogenic cysts. The diagnosis of the development of carcinoma from the cyst lining can only be established by histopatologic examination. Report: A case of SCC arising from a mandibular residual cyst in a 55-year-old man is presented along with a discussion of the critical elements needed for accurate diagnosis and treatment. Summary: The development of SCC from residual cysts is rare but should always be considered in the differential diagnosis. This case report clearly demonstrates the importance of clinician awareness of the malignant potential of apparently innocuous cystic lesions. It also underscores the importance of a careful histological examination and the necessity of obtaining biopsy materials from various areas to prevent a misdiagnosis of large-sized cysts.