Background: Nasopharyngeal cancer (NPC) is characterized by a distinct geographic distribution which reflects genetic predispositions, with highest incidence in Southeastern Asia and Southern China. It continues to cause a significant health burden among Asian Americans (AAs), which is a fast growing but understudied racial group. Prior studies investigating NPC combined all AA groups which may mask heterogeneities among AA subgroups. We aimed to examine the disparities in NPC by dividing AAs into four major ethnic groups - Chinese, Filipinos, Vietnamese, and Japanese Americans. Methods: NPC cases were identified from the Surveillance, Epidemiology, and End Result (SEER) 18 database from 1975-2016. Information regarding age, sex, race/ethnicity, education, income, % of foreign born, marital status, region of SEER registry, stage, histology, grade, surgery, chemotherapy, and radiation therapy were extracted. Multivariate-adjusted Cox proportional hazard regression and Fine-Gray sub-distribution hazard models were used to calculate overall and cause-specific mortality. SEER*Stat was used to calculated age-adjusted incidence. Results: Among a total of 11,737 NPC patients, 42.2% were non-Hispanic White (NHW), 10.7% non-Hispanic Black (NHB), 7.1% Hispanics, 18.9% Chinese, 7.6% Filipinos, 4.8% Vietnamese, 1.0% Japanese and 7.7% other Asians. AAs continue to have the highest NPC incidence among all racial groups despite of an overall decreasing trend. Japanese were significantly more likely to be diagnosed at localized stage, having low grade tumor and having keratinizing squamous cell carcinoma histology compared to other AAs. Compared to NHW, Filipino Americans had decreased mortality (HR = 0.90; 95%CI:0.84-0.98). Chinese (HR = 0.95; 95%CI: 0.90-1.01), and Vietnamese (HR = 0.94; 95%CI: 0.86-1.03) also observed marginally reduced mortality but not Japanese Americans (HR = 1.09; 95%CI: 0.90-1.32). No differences in NPC-specific mortality by race/ethnicity groups were found. In addition, Chinese, Filipino and Vietnamese Americans with NPC were less likely to die of other cancer and cardiovascular disease than NHW, but no such differences were observed among NHB, Hispanics or Japanese Americans. Conclusions: Asian Americans have been historically studied as one single racial group mostly due to limited sample size, despite that it is consistent of a diverse population with different genetic makeup, socioeconomic status, cultural background, health behaviors, and health care access. Our novel finding that significant disparities exist within AA NPC patients in regard to demographic and clinical features, overall and cause-specific mortality underlines the importance of adequate AA-subgroup specific sample size in future studies in order to understand the prognostic role of ethnicity in NPC, and advocates more ethnically and culturally tailored cancer care delivery.