The case of a 50 years old male patient with CML is presented herewith whose diagnosis revealed clonal evolution (+8) of a Ph+ clone. Although the treatment with a second generation TKI (nilotinib) had resulted a deep molecular remission and elimination of the Ph+ clonal proliferation, appearance of clonal evolution of a Ph– clone was observed at the upcoming 30th month of the medication. The acquired 5q- and 7 monosomy clone resulted in MDS with a severe pancytopenia and a serious need for massive hemosupportation. Afterwards, the patient had refused an offer for allogenic stem cell transplantation and lenalidomide treatment was initiated. Due to a massive run of these treatments for 8 months the non-MDS Ph– clone ploriferation reappeared and the patient was not requiring hemosupportation for a while. However, after the following 4 month period of calm the patient became pancytopenic again, as the MDS clone had returned, and the emerging neutropenic sepsis eventually resulted in fatal outcome.