The nasopharyngeal carcinoma (NPC) incidence has marked variation among geographical areas. It is less than 1 per 100,000 persons per year for either sex in most countries in the world. However, the age-standardized incidence rate is extremely high in southern China and Southeast Asia. NPC is also a common cancer in Taiwan with the age-standardized incidence rate for males and females in 2007 of 8 and 3 per 100,000, respectively. Epstein–Barr virus (EBV) infects over 90 percent of the population worldwide and usually with lifelong persistence. The disease burden due to EBV is enormous. NPC is one of the malignancies linked to EBV infection, and numerous studies have shown both diagnostic and prognostic utility of EBV antibody (anti-EBV) testing for NPC. A long-term follow-up study in Taiwan found both anti-EBV VCA IgA and anti-EBV DNase are important predictors of incident NPC over an average follow-up period of 16 years. Compared with participants seronegative for both anti-EBV markers as the referent group, the hazard ratio (95% confidence interval [CI]) of developing NPC was 4.0 (1.6-10.2, P=0.003) and 33 (7.3-147.2, P<0.001), respectively, for participants seropositive for only one and both seromarkers. As the anti-EBVs were tested using specimens collected years before NPC diagnosis, the study findings give credence to an etiologic role of EBV in NPC pathogenesis, and argues against EBV acting simply as a passenger virus that reactivates after NPC development. Sufficient evidence is available to conclude that EBV infection causes NPC. It is time to accelerate the research and development of preventive EBV vaccine for reduction of the risk of primary EBV infection and NPC.