The etiology of NPC is multifactorial and includes virological, genetic, and environmental factors as described. These factors can be synthesized into a model for the development of NPC through a multistep process. First, an individual may carry a genetic predisposed risk of developing NPC as suggested by the HLA linkage of the disease. The nasopharyngeal epithelium becomes infected early in life by EBV and viral gene expression eventually becomes limited to EBNA-1, LMP1, LMP2A/2B, and perhaps another viral protein not yet fully characterized. LMP1 has profound growth stimulating effects in vitro and may exert similar effects in the nasopharyngeal epithelium. As cells are stimulated to divide, the presence of EBNA-1 ensures that the viral genome will replicate and be distributed to progeny cells. Finally, to reach their full malignant potential, the dividing nasopharyngeal cells may acquire cellular genetic changes involving recessive TSGs on chromosome 3. The risk for developing secondary genetic alterations involving these genes may be increased by exposure to environmental carcinogens such as volatile nitrosamines in salted fish. Thus, NPC provides a model system for understanding the interactions of genetic, infectious, and environmental factors involved in oncogenic transformation. Recent developments in organoculture systems and transgenic animal technology should allow dissection at the molecular level of the specific mechanisms involved in this process.