BCR-ABL tyrosine-kinase inhibitors are the first-line therapy for the majority of patients with chronic myelogenous leukemia (CML). Up to 20% of patients who have imatinib-treated CML in blast crisis (BC) experience a relapse in the central nervous system (CNS) due to the poor penetration of the drug by the blood-brain barrier. The present case reports a successful experience of using dasatinib-based combination therapy to treat a 22-year-old female who presented with initial symptoms of intermittent fever and easy bruising under the diagnosis of CML in BC. Although the patient eventually succumbed to profound sepsis, the CNS involvement was treated successfully using dasatinib-based combination therapy (cranial radiation and de-escalated intrathecal chemotherapy). This case demonstrates that dasatinib may be a viable option for those who are not medically fit for or are otherwise unwilling to receive high-dose chemotherapy. It appears that dose intensity is essential for optimal efficacy and should be maintained at 150 mg daily as far as possible.