Febrile neutropenia (FN) is a complication of hematologic malignancy therapy. An early diagnosis would allow optimization of antimicrobials. The F-FDG-PET-CT may be useful; however, its role is not well established. We analyzed retrospectively patients with hematological malignancies who underwent F-FDG-PET-CT as part of FN management in our university hospital and compared with conventional imaging. In addition, we performed a systematic review of the literature assessing the usefulness of F-FDG-PET-CT in FN. A total of 24 cases of FN underwent F-FDG-PET-CT. In addition, 92% had conventional CT. In 5/24 episodes (21%), the fever was of infectious etiology: two were bacterial, two were fungal, and one was parasitic. When compared with conventional imaging, F-FDG-PET-CT had an added value in 20 cases (83%): it diagnosed a new site of infection in 4 patients (17%), excluded infection in 16 (67%), and helped modify antimicrobials in 16 (67%). Antimicrobials could be discontinued in 10 (41.6%). We identified seven publications of low quality and one randomized trial. Our results support those of the literature. The available data suggest that F-FDG-PET-CT is useful in the management of FN, especially to diagnose fungal infections and rationalize antimicrobials. This review points out the low level of evidence and indicates the gaps in knowledge.