Epstein-Barr virus (EBV) is a ubiquitous herpes virus and often causes acute infectious mononucleosis (IM) in immunocompetents. Chronic active EBV infection (CAEBV) is diagnosed with recurrent IM like symptoms and unusual pattern of anti-EBV antibodies or increased EBV genomes after exclusion of other chronic known disease. We presented a boy with CAEBV who progressed hemophagocytic lymphohistiocytosis (HLH) due to NK cell neoplasm. A 19 year-old adolescent boy was admitted due to fever. He was always developed IM like symptoms after mosquito bite, as high fever with skin necrosis at mosquito bite site since 6 year of age. He was diagnosed with IM due to EBV at that time. However, he was developed recurrent IM with mosquito bite skin necrosis. We diagnosed with CAEBV, that showed atypical lymphocytosis in peripheral blood and non-specific bone marrow (BM) findings, and flow cytometery showed 78.1% of CD56, 18.4% of CD3, 6.3% of CD19 with positive anti-VCA IgG and EBNA IgG at 8 year of age. His EBV copy number was increasing for several years. He experienced mild symptoms during steroid and cyclosporine (CSA) for 2 years. The genetic study including lymphoproliferative disorders and XMEN disease was negative. We recommended hematopoietic stem cell transplantation (HSCT) with identified HLA matched sister, but parents refused because he was well-being except mosquito bite event. At admission, laboratory data was compatible with HLH including cytopenia, high ferritin, hypofibrinogenemia, and hypertriglyceridemia with high titer of EBV genome. BM study showed hemophagocytosis with 46, XY, del (4) (q25q31.1), and flow cytometry for BM showed CD3(+), cy-CD3(+), CD5(+), CD8(+), CD45(+), CD43(+), CD56 (+) compatible to NK cell neoplasm. He improved symptoms and laboratory data after steroid and CSA. He was re-admitted due to knee joint pain and fever 3 weeks later. The symptoms and laboratory data showed as recurrent HLH. However, he was rapidly progressed to pulmonary infection due to pneumocystis jiroveci and expired in spite of aggressive therapy. In our case, we suggested that CAEBV infection might have to be treated with HSCT before aggressive EBV manifestations.