Hemophagocytic lymphohistiocytosis is a condition of immune dysregulation characterized by severe organ damage induced by a hyperinflammatory response and uncontrolled T-cell and macrophage activation. Secondary hemophagocytic lymphohistiocytosis typically occurs in association with severe infections or malignancies. Patients with acute myeloid leukemia may be prone to develop hemophagocytic lymphohistiocytosis because of an impaired immune response and a high susceptibility to severe infections. In a series of 343 patients treated by intensive chemotherapy over a 5-year period in our center, we identified 32 patients (9.3%) with fever, very high ferritin levels, and marrow hemophagocytosis (i.e. patients with hemophagocytic lymphohistiocytosis). Compared to patients without hemophagocytic lymphohistiocytosis, these 32 patients had hepatomegaly, pulmonary or neurological symptoms, liver abnormalities, lower platelet count and higher levels of C-reactive protein as well as prolonged pancytopenia. A microbial etiology for the hemophagocytosis was documented in 24 patients: 14 bacterial infections, 9 Herpesviridae infections and 11 fungal infections. The treatment of hemophagocytic lymphohistiocytosis consisted of corticosteroids and/or intravenous immunoglobulins along with adapted antimicrobial therapy. Patients with hemophagocytic lymphohistiocytosis had a median overall survival of 14.9 months, which was significantly shorter than that of patients without hemophagocytic lymphohistiocytosis (22.1 months) (P=0.0016). Hemophagocytic lymphohistiocytosis was significantly associated with a higher rate of induction failure, mainly due to deaths in aplasia. Hemophagocytic lymphohistiocytosis can be diagnosed in up to 10% of patients with acute myeloid leukemia undergoing intensive chemotherapy and is associated with early mortality. Fever, very high ferritin levels and marrow hemophagocytosis represent the cornerstone of the diagnosis. Further biological studies are needed to better characterize and recognize this syndrome in patients with acute myeloid leukemia.