Distinguishing between acquired aplastic anemia (AA) and myelodysplastic syndrome (MDS) with a low blast cell percentage is often difficult and problematic, as both diseases are syndromes primarily defined by morphological findings, and their diagnostic criteria do not necessarily reflect the pathophysiology of their bone marrow (BM) failure. As a result, many patients with benign BM failure that should be managed as AA are diagnosed as having MDS, due to the absence of BM hypocellularity and the presence of dysplastic signs in the BM, and are treated inappropriately with toxic therapies, such as hypomethylating agents, and stem cell transplantation from unrelated donors. BM failure syndromes need to be managed in ways appropriate to their pathophysiology, which is more accurately determined by using markers such as the presence of glycosylphosphatidylinositol-anchored protein-deficient cells and HLA-A lacking leukocytes. We recently found that plasma thromobopoietin level is one of the most useful markers for distinguishing benign and pre-leukemic BM failure syndromes.