Myeloid sarcoma is an extramedullary tumor of immature granulocytic cells. It is a rare condition, most often associated with acute myeloid leukemia (AML), although in some rare cases it may present in nonleukemic patients. It should therefore be considered as a differential diagnosis of any atypical cellular infiltrate. It may occur at any site, leading to very varied clinical presentations. Diagnosis is challenging and relies on a high index of suspicion as well as radiology, histology, immunophenotyping, and molecular analyses, which also are essential for risk stratification and treatment planning. Systemic chemotherapy using AML-like regimens should be commenced early, even in nonleukemic disease. Surgery and/or radiotherapy may be indicated for symptomatic lesions or tumors causing local organ dysfunction or obstruction. Allogeneic hematopoietic stem cell transplantation has demonstrated promising results, particularly in patients who achieved complete remission with AML-induction protocols, and recent advances in genetic profiling may enable the development of novel targeted therapies. Prospective multicenter controlled trials are required to further refine management decisions and investigate the role of novel targeted therapies.