Aggressive natural killer cell leukemia (ANKL) is a rare malignant disorder of mature NK cells characterized by aggressive clinical course and poor outcome. The commonly involved sites are peripheral blood, bone marrow, liver, and spleen, but any organ can show involvement. We report a case of ANKL diagnosed and assessed the clinical response with 18F-FDG PET. Pretreatment and posttreatment FDG PET/CT showed a high correlation with pathologic diagnosis and staging as well as in the follow-up assessment of the clinical response. FDG PET could be a valuable tool enabling comprehensive staging and follow-up of ANKL.