A patient whose chronic myelogenous leukemia (CML) was treated with interferon alpha (IFN-α) is described. The disease showed karyotypic evolution during the chronic phase and the later myeloid acceleration. Both of these secondary clonal phenomena responded to IFN-α dose escalation. The case illustrates the dose dependence of CML responses to IFN-α. The phenomenon of clonal evolution is discussed in the context of this patient’s disease.