Acquired pure red cell aplasia (PRCA) can be primary or secondary to other diseases. PRCA association with chronic myelomonocytic leukemia (CMML) is very rarely reported. Although treatment is directed to underlying cause in secondary PRCA treatment, optimal treatment in patients with CMML and PRCA is unknown, because only four case reports are available. In addition, the effect of hypomethylating agents can be detrimental due to myelosuppression, at least in the early phase of treatment. Bone marrow examination of a 66-year-old woman with severe anemia revealed PRCA and was suspicious for CMML. There was no HLA-matched sibling for bone marrow transplantation. The patient received immunosuppressive therapy with steroids and cyclosporine with temporary response in anemia; however, progressed to acute leukemia over 8 months and died. Immunosuppressive therapy in patients with CMML and PRCA should be cautiously used because it may accelerate acute leukemia transformation.