Translocation t(3;21)(q26;q22) is a rare but nonrandom event occurring in Philadelphia positive chronic myeloid leukemia. We describe five new cases (two males, three females) where t(3;21) is associated with the progression of the disease. Using FACS analysis, we confirm the myeloid type of the blast crisis. High resolution chromosomal analysis allowed us to define more precisely the chromosomal breakpoints to 3q26.2 and 21q22.2, close to the respective localizations of two genes important in cell proliferation and cancer pathogenesis: the transferrin receptor gene and the ets.2 proto-oncogene.