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PURPOSE Osteosarcoma occurring in the head and neck region is known as a malignant tumor that shows a relatively poor prognosis and, despite various treatments, clinicians have often been confounded by it. The existence or non-existence of the mutation of the gene p16INK4a has been used in prognosis assessment. In this study, author have attempted to determine whether methylation of the gene p16INK4a could be applied to forecast the progress of osteosarcomas in the head and neck region having been given poor prognoses in the diagnostic process and the early stage of treatment. RESEARCH SUBJECT AND METHOD Clinicopathologic investigations, immunohistochemical examinations, a methylation specific polymerase reaction (MSP) analysis, and a survival analysis were conducted on the tissues of 20 patients with mandibulofacial osteosarcoma. RESULTS Neither age, sex, size, smoking or non-smoking, nor region have showed a statistical significance with methylation or unmethylation of the gene p16INK4a and expression rates demonstrated by immunohisto- chemical examinations. A chi-square test indicated that recurrence inclination has no relation with the expression rate of p16 protein (p=0.6615), but it showed a statistical significance with methylation of the gene p16INK4a (p=0.0033). With respect to investigations of the survival rates, a Kaplan-Meier survival analysis found that the manifestation rate of p16 protein did not have an impact on survival (p=0.8864), but that the methylation of the gene p16INK4a resulted in significant differences in survival rates (p=0.0105). CONCLUSIONS The above results show that methylation of the gene p16INK4a could be one of the major factors that help determine the recurrence inclination and prognosis of osteosarcomas occurring in the head and neck region.