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Approximately 90% of all head and neck malignancies and 94% of oral malignancies are squamous cell carcinoma (SCC). Tobacco smoking is considered as the most important causative agent for SCC. Despite aggressive and multidisciplinary treatment approaches, there has been no significant improvement in 5-year survival over the past 20 years. Several prognostic and predictive clinical, pathological and molecular factors have been introduced for SCC. We herein review some of these prognostic factors.