Sudden blast phase (SBP) is a rare event that occurs in an unpredictable fashion amongst patients with chronic myeloid leukemia (CML) who otherwise appear to be responding satisfactorily to imatinib (IM) treatment. We investigated the incidence, clinical characteristics, treatment outcome and long-term follow-up of 213 patients with chronic phase CML treated with IM according to the European LeukemiaNet guidelines. Nine patients, eight of whom received IM as first-line therapy, developed SBP (4.2% of the total). They tended to have low or intermediate risk Sokal scores at diagnosis, a predominance of the lymphoid phenotype and a short interval from "optimal" response to the development of BP. Five of the nine patients with SBP are alive in complete molecular remission; however, all of them underwent allogeneic hematopoietic stem cell transplant. The cumulative incidence of SBP for the patients who received IM as first-line therapy was 5.9% and the 2-year overall survival of the nine patients who developed SBP was 56%. Despite the improved outcome for patients with SBP receiving tyrosine kinase inhibitors (TKIs) and transplant, many of these patients are not salvaged with these therapies. This illustrates the need to develop predictive models to identify patients early whose response to TKI therapy will not be durable and hopefully prevent the transformation to advanced disease.