Hyperleukocytosis, a white blood cell count greater than 100,000/mcl, can be associated with the following three primary oncologic emergencies: leukostasis, disseminated intravascular coagulation, and tumor lysis syndrome. These complications significantly increase a patient’s risk of morbidity and mortality. Therefore, timely evidence-based interventions ensure patient safety. This article provides clinical evidence and guidelines for advanced practice nurses working in hematology-oncology to support diagnostic workup and management of hyperleukocytosis in patients with acute myeloid leukemia. A patient case study demonstrates key concepts.