Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm of hematopoietic cell origin.It arises from the translocation of chromosomes 9 and 22, with resultant Philadelphia (Ph) chromosome that contains the BCR-ABL1 gene.CML has three phases: the chronic phase, the accelerated phase, and blast crisis. Tyrosine kinase inhibitors are used as the targeted therapy of CML. This report is about a 30-year-old male who is normally fit and well with no past medical history of note. He was diagnosed previously with CML and presented in a blast crisis. With this blast crisis at presentation, the patient was started on ponatinib. After 12 days from starting ponatinib, the patient presented with abdominal pain and vomiting. Imaging showed small bowel perforation, which required immediate surgery. The patient's cardiovascular risk for such event was low and ponatinib was thought to be the most likely cause of this complication; thus, higher-risk patients for such ischemic events should be observed closely.