Background: Although myelodysplastic syndromes are heterogeneous disorders comprising a benign subset of bone marrow failure similar to aplastic anemia, no laboratory test has been established to distinguish it from bone marrow failures that can evolve into acute myeloid leukemia. Design and Methods: Plasma thrombopoietin levels were measured in 120 patients who had myelodysplastic syndrome with thrombocytopenia (< 100 x 109/L) to determine any correlation to markers associated with immune pathophysiology and outcome. Results: Thrombopoietin levels were consistently low for patients with refractory anemia with excess of blasts, while patients with other myelodysplatic syndrome subsets had more variable results. Patients with thrombopoietin levels ≥320 pg/mL had increased glycosylphosphatidylinositol-anchored protein-deficient blood cells (49.1% versus 0%), were more likely to have a low International Prognostic Scoring System (IPSS) score (≤1.0, 100% versus 65.5%), a higher response rate to immunosuppressive therapy (84.2% versus 14.3%), and a better 5-years progression-free survival rate (94.1% versus 63.6% for refractory cytopenia with unilineage dysplasia; 100.0% versus 44.4% for refractory cytopenia with multilineage dysplasia). Conclusions: Increased plasma thrombopoietin levels were associated with a favorable prognosis of bone marrow failure and could therefore represent a reliable marker for a benign subset of myelodysplastic syndrome.