The introduction of tyrosine kinase inhibitors (TKI) in the treatment of Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) has revolutionized the outcome, but the prognosis of the disease is still based on prognostic systems that were developed in the era of conventional chemotherapy and interferon (IFN)-alfa. A new prognostic score including only two variables, spleen size and basophils, was developed for the prediction of complete cytogenetic response (CCyR) and progression-free survival (PFS). The score was based on a large series of patients who were enrolled in prospective multicenter studies of first-line imatinib treatment. The prognostic value of the EUTOS (European Treatment and Outcome Study for CML) score has now been tested in an independent, multicenter, multinational series of 1288 patients who were treated first-line with imatinib outside prospective studies. It was found that also in these patients, the EUTOS prognostic score was predictive for CCyR, PFS and overall survival (OS). In addition, the prognostic value of the score was reported to be significant in seven of the eight other independent studies of almost 2000 patients that were performed in Europe, the Americas and Asia. The EUTOS risk score is a valid tool for the prediction of the therapeutic effects of TKI, particularly imatinib.