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FDG PET/CT was performed in a 30-year-old woman to detect the source of fever of unknown origin. The images showed widespread abnormal activity, consistent with lymphoma. However, lymph node biopsy revealed only inflammation, and a diagnosis of familial hemophagocytic lymphohistiocytosis was eventually made after familial hemophagocytic lymphohistiocytosis–specific gene was detected. After proper therapy, a follow-up FDG PET/CT examination 2 months later showed resolution of most of the previously seen lesions.