Since its description in 1961, the Phila delphia (Ph) chromosome has been a sym bol and a paradigm of malignancy, because all Ph chromosomepositive leukemia resulted in the death of the patients, either in months or in years [1]. The Ph chromo some was originally described as a derivative of chromosome 22, due to a partial deletion of the long arm of that chromosome. Then, it was shown that there was not a deletion, but a reciprocal translocation of a part of the long arm of chromosome 22 into the long arm of chromosome 9, and vice versa, (t[9;22]; q2.2;q 1.1), leading to a loss of a variable part of chromosome 9 and to the formation of a new gene on chromo some 22, due to the fusion of cABL from chromosome 9 with BCR (coding for a ser ine–threonine kinase) on chromosome 22. The new fusion gene, BCR–ABL, is located in the cytoplasm, is a constitutively acti vated tyrosine kinase (TK), and activates several downstream signals that affect cell proliferation and maturation, leading to the leukemic transformation of hemopoietic cells [1–4]. This results in an uncontrolled proliferation of the hemopoietic tissue in the bone marrow, in the spleen and in the liver, with leukocytosis and circulating progenitors – the clinical and hemato logic picture of chronic myeloid leukemia (CML), as it was described by Bennett and Virchow more than 150 years ago [1,3]. The BCR–ABL gene is not only respon sible for the expansion of the myeloid tis sue, but causes a genetic instability, whose molecular mechanisms have not yet been elucidated, that leads to further genomic alterations, resulting in the acquisition of an acute leukemialike phenotype that is resistant to any treatment and leads inex orably to death [1–4]. While the molecular bases of Ph chromosomepositive CML are well known, the causes are unclear. On one hand, we know that BCR–ABL can be generated in vitro upon experimen tal exposure to radiation, and that the atomic bomb explosions in Hiroshima and Nagasaki caused an excess number of cases of CML [1,3]. But, on the other hand, BCR–ABL is exceedingly rare in the cases of leukemia secondary to radia tion and cytotoxic agents, and although the frequency of CML increases with age, as it does for most cancers, the Ph chro mosome is never found in acute myeloid leukemia and myelodysplastic syndrome, which are so frequent in the elderly.