Objective To explore prospective diagnostic criteria for preleukemia.Methods A case control study was done comparing the discrepancies on clinical and laboratory features between patients with preleukemia and those with chronic aplastic anemia (CAA) or atypical paroxysmal nocturnal hemoglubinuria (a-PNH).Results There were eight variables of significance: (1) lymphocytoid micromegakaryocytes in the bone marrow; (2) immature granulocytes in the peripheral blood; (3) ≥2.0% myeloblasts in the bone marrow; (4) positive periodic acid schiff (PAS) stained nucleated erythrocytes; (5) myeloid differentiation index ≥1.8; (6) typical colonal karyotypic abnormalities; (7) negative sister chromatid differentiation; (8) cluster/colony ratio of granulocyte-macrophage colony-forming units (CFU-GM)>4.0. The following criteria were assigned: A: to meet variable one and at least two of the other seven variables and B: to meet at least four of the eight variables. All of the patients with preleukemia met either A or B and none of the patients with CAA or a-PNH did. Conclusions Preleukemia is different from CAA or a-PNH. It has its own clinical and laboratory features, which may be useful for its prospective diagnosis.