Florid cemento-osseous dysplasia is an extensive form of periapical cemental dysplasia, which usually involves 1 to 4 posterior areas of the maxilla and mandible. The affected area undergoes changes from normal vascular bone into an avascular cementum-like lesion. The lesion is usually benign; however, treatment of a secondary infection of this lesion can be difficult and complicated. This clinical report describes a rare but aggressive secondary infection of this type, which was successfully treated by a combination of complex surgical and prosthodontic procedures, including dental implant therapy.