IntroductionEBV is a ubiquitous pathogen implicated in various clinical syndromes, including malignancies such as nasopharyngeal carcinoma, Burkitt lymphoma, and post-transplant lymphoproliferative disorders.2 While its association with acute leukemia is rare, EBV’s role in leukemogenesis, particularly in pediatric patients, remains an area of growing interest due to its complex interplay with immune dysregulation and host genetics.3AML in children is a heterogeneous malignancy, and its management becomes even more challenging when complicated by secondary HLH. HLH is a life-threatening hyperinflammatory syndrome triggered by infections, malignancies, or immune dysregulation, with EBV being a well-recognized precipitant.4 EBV-driven HLH is particularly severe, as the virus evades immune surveillance, leading to unchecked immune activation, cytokine storm, and potential multiorgan failure.5 Early recognition and aggressive treatment with immunosuppressants, chemotherapy, and targeted antiviral therapies are critical for improving outcomes.This case report describes a rare presentation of EBV infection in a previously healthy adolescent with newly diagnosed AML and secondary HLH. It highlights the diagnostic complexities of managing concurrent malignancy and immune dysregulation, emphasizing the need for a multidisciplinary, individualized approach to optimize patient outcomes.