Orofacial malignant tumors are the sixth most common malignancy in the world and, with pharyngeal malignancies, the third most common one in the developing world. This study was carried out to determine the malignant oral primary tumors in Shiraz, southern Iran. From April 2002 to March 2007, all (181) malignant tumors of the orofacial region recorded in Fars Cancer Registry Center of Shiraz University of Medical Sciences in Shiraz, southern Iran, were enrolled. Age range of patients was 4 to 91 years (53.7 +/- 18.6 years), whereas 40% of cases were older than 60 years. Ninety percent were epithelial tumors, 6% sarcomas, and 4% lymphomas. The most common sites were tongue (34.3%) and major salivary glands (32.5%). Squamous cell carcinoma (50.8%) was the most common malignant orofacial tumor. Oral malignant tumors were more common in males than females with an older aged preponderance. The tongue was the most commonly affected site, and squamous cell carcinoma was the most common malignant orofacial tumor. There is an urgent need for a national program focusing on early detection of these tumors. Oral health professionals in Iran should be educated on oral cavity comprehensive examination because of the important role of dentists in early detection of malignant oral tumors.