Epstein-Barr virus (EBV)-associated nasopharyngeal carcinoma (NPC) generally occurs in adults, especially in high-prevalence populations such as the Chinese and Eskimos. In Maghrebian populations, young patients affected with this malignancy represent 25% of the total NPC cases. In adults with NPC, relatively high titers of IgA antibodies to the EBV viral capsid antigen (VCA) and early antigen (EA) represent important markers. However, nearly 50% of young NPC patients are negative for IgA-anti-VCA and -EA or exhibit very low titers of these antibodies. We report here that 92% of sera from young NPC patients negative for IgA-EA and 89% of those negative for IgA-VCA were positive for IgG antibodies to the EBV transactivator protein (ZEBRA) at very high titers. Our results show that in young patients with NPC these antibodies represent the most reliable marker for diagnosis and prognosis, particularly when compared with conventional NPC markers, i.e., IgA-VCA (58%) and anti-EA (25%). The titers of IgG-ZEBRA antibodies increased along with lymph node involvement only in the young patient group, suggesting a prognostic value of this marker in this patient group.