Imatinib mesylate (tested as STI571), an abl kinase inhibitor, induces sustained, complete hematologic and cytogenetic responses in chronic myelocytic leukemia (CML) patients; however, emergence of clonal chromosomal aberrations in Philadelphia-negative (Ph-) cells during treatment has been reported. We describe two CML patients in chronic phase who presented with complete cytogenetic responses during imatinib mesylate therapy but developed new clonal chromosomal rearrangements in Ph- cells. The first patient presented with a duplication of chromosome 1, dup(1)(q21q42), and the second showed two new clonal aberrations consisting of inv(1)(q12q32) and del(7)(q22) in the same clone.