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Introduction: Asthma and hypereosinophilia have been treated with different therapeutics in the past. Some of them appear to be more effective in symptoms resolution and decreasing eosinophilic count. Case Presentation: We report here an unusual case of asthma with hypereosinophilia secondary to Chronic Myeloid Leukemia (CML) with high prevalence of eosinophilic infiltrate, treated simultaneously with an anti-IL-5 antibody (Mepolizumab) and Tyrosine-kinase Inhibitors (TKI: Imatinib and Bosutinib) for three years. The patient showed a promising reduction of pulmonary exacerbations and good control of CML without developing side effects. Conclusion: We hope that this finding could inspire further studies on the efficacy and safety of the concomitant use of anti-IL-5 and TKI.