We experienced a rare case of oral squamous cell carcinoma arisen from gingival tissues overlying prolonged chronic osteomyelitis of the mandible. A 66 years old man complained of unhealed extraction sockets of left mandibular second premolar and first molar, and showed extensive leukoplakia in the gingival tissues of the same area. The inflammation of the socket granuloma became severe and extended into adjacent mandibular proper, resulted in diffuse suppurative chronic osteomyelitis of mandibular body, exhibiting irregular osteolytic changes of mandibular trabecular patterns in mottled radiolucent appearance. The leukoplakia was initially diagnosed under microscope, and the involved gingival tissues were radically removed. Thereafter, the gingival soft tissue inflammation involving the mandibular osteomyelitis was hardly healed for two years. During the period of repeated surgical treatments for the inflamed lesion, nine biopsies were taken sequentially. Until the eighth biopsy, there consistently showed the suppurative osteomyelitis with ingrowing gingival tissues into the bony inflammatory lesion. The gingival epithelium showed the features of leukoplakia but no evidence of malignant changes. However, the ninth biopsy, taken about 2 years after initial diagnosis, showed the early carcinomatous changes of the gingival epithelium. The neoplastic epithelial cells were relatively well differentiated with many keratin pearls, and infiltrated only into underlying connective tissues. So, we presumed that the present case of squamous cell carcinoma was caused by the persistent inflammatory condition of the mandibular osteomyelitis, and also suggest that the leukoplakia should be carefully removed in the beginning to prevent the neoplatic promotion of the chronic inflammation.