We describe a case of a patient affected by a chronic myeloproliferative disorder with t(8;21)(q22;q22) and trisomy 8 at diagnosis. At the time of blastic metamorphosis, 2 months later, trisomy 8 metaphases were significantly reduced, while a predominance of t(8;21) was present. Finally, in the phase of leukemic regrowth following chemotherapy administration, monosomy 8 associated with der(21)t(8;21) was the predominant cytogenetic abnormality.