Ponatinib is a third-generation tyrosine kinase inhibitor (TKI) which is used as a chemotherapeutic agent in the treatment of chronic myeloid leukemia. Despite being relatively less toxic than other older TKIs, it still has various adverse effects including skin rash. Cutaneous manifestations have varied presentations such as lichenoid, pityriasiform, ichthyosiform, and pityriasis rubra pilaris-like rash. We present here a 35-year-old male with chronic myeloid leukemia who developed a unique pattern of symmetrical rash to Ponatinib which was successfully treated with topical tacrolimus and reduction of dose of the drug.