ObjectiveTo report and analyze one case of Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) initially presented with skeletal destruction treated with imatinib-based personal therapy. MethodsWe described the therapeutic advancements for ALL cases initially presented as skeletal destruction and Ph+ ALL through case report and literature review. ResultsDefinite diagnosis of Ph+ ALL was made for the patient who subsequently obtained inductive remission and 17-month molecular remission with the aid of imatinib-based regimen. ConclusionWe should take potential diagnosis of ALL into consideration for patients with skeletal destruction. Imatinib-based standard chemotherapeutic regimen may improve therapeutic model and prognosis of Ph+ ALL.