Background: Pandemic influenza A/H1N1/2009 virus usually causes mild illness in healthy children. Chronic medical conditions are recognized as increasing the risk for complications of influenza virus infection. Although most studies including children with acute leukemia and H1N1 virus have reported no deaths, some anectodal reports with low patient numbers have reported mortality rates as high as 28.5%. Here, we report patients with leukemia and H1N1 virus and review the literature. Methods: Medical records of all children with leukemia and H1N1 virus in our institution were reviewed for demographic, clinical, and laboratory data. We also carried out a systematic review of the English-language literature. Among the 24 articles found, only patients with leukemia and pandemic H1N1 infections were reviewed by two independent reviewers. Results: Eight of 98 children who received chemotherapy for leukemia were diagnosed with pandemic H1N1 infection. One developed pneumonia and acute respiratory distress syndrome (ARDS) and died. Another one developed hemophagocytic lymphohistiocytosis (HLH) and died due to secondary infection during the 6th week of treatment for HLH. In our study, 2 of 8 patients had a fatal course (25%), compared with an overall mortality of 2.5% in the studies retrieved from PubMed (6/232). Conclusion: Pandemic H1N1 influenza virus caused mortality in patients with ARDS or HLH; an unexpected finding for pandemic H1N1 (2009) influenza virus. Thus, for children with leukemia and infected with H1N1 virus, short-and long-term complications should be kept in mind during evaluation.