Objective To study the clinical characteristics, diagnosis and treatment strategy of oral and maxillofacial malignancies in multiple primary malignant neoplasms(MPMNs). Methods 21 cases of oral and maxillofacial malignancies associated with MPMNs admitted to our hospital between 1985 and 2000 were studied respectively. Results There were 44 malignant cases in the 21 MPMNs patients. Among the 44 cases, there were 24 cases in alimentary and respiratory tract such as oral, pharynx, esophagus, stomach and lung, and 10 cases in salivary gland, breast and female reproductive system. There were 25 cases malignant neoplasms in oral and maxillofacial region where squamous cell carcinoma was the most common pathologic type, secondly adenoid cystic carcinoma. In oral and maxillofacial region, MPMNs were often found in tongue, parotid and submandibular gland, buccal mucosa and gingival. Conclusion Tongue and salivary gland were the common locations with MPMNs, and they were closely associated with alimentary and respiratory tract. Patients with malignancies of oral and maxillofacial region associated with MPMNs must be submitted to a long-term and careful follow-up. For female patients, breast and female reproductive system should be examined specially. Regular follow-up, early detection, early diagnosis, active and effective treatment can help to improve the survival quality of MPMNs patients.