A 51-year-old man had been diagnosed with severe aplastic anemia (AA) at the age of 9 years. He was treated with occasional transfusions for the next 35 years. Following initiation of cyclosporin A (CsA), the patient became transfusion-independent at 44-years-old. Anemia improved after cessation of CsA and no therapy was required for the next 5 years. However, severe pancytopenia suddenly developed at the age of 51. Bone marrow aspiration revealed myelodysplastic syndrome (MDS) with der (1;7). The ineffectiveness of CsA for MDS led to resumed dependence on transfusion. This case suggests that the appearance of MDS clones might have contributed to transient hematological improvement. Bone marrow aspiration should be considered in patients with AA if unexpected hematological improvement appears.