Squamous cell carcinoma (SCC) is the most common malignant tumor in the oral cavity, and it accounts for about 90% of all oral cancers. Several risk factors for oral SCC have been identified; however, SCC associated with odontogenic keratocysts have rarely been reported. The present study describes the case of a 36-year-old man with SCC of the right ramus of the mandible, which was initially diagnosed as a benign odontogenic cyst. He underwent enucleation at another hospital followed by segmental mandibulectomy and fibular free flap reconstruction at our institution. In this case, we introduce a patient with oral cancer associated with odontogenic cyst on the mandible and report a satisfactory outcome with wide resection and immediate free flap reconstruction.