The risk of second malignant neoplasms (SMN) in chronic myeloid leukemia (CML) survivors remains unclear. We utilized the Surveillance, Epidemiology and End Results 18 (SEER 18) registries to evaluate the risk and subsequent outcomes of SMN in CML survivors. There were 3407 patients included. Of these, 170 (4.99%) developed a SMN with SIR of 1.40 (95% C.I. 1.19–1.62). An increased risk was noted for cancers of the respiratory tract, genitourinary (GU) tract and skin excluding basal cell and squamous cell carcinoma. Using 3:1 matching (3 de novo malignancies to 1 post-CML SMN case), we compared survival data for cancers of the respiratory, GU and gastrointestinal (GI) tract. Patients with GU malignancies developing after CML had worse overall survival than patients without prior CML diagnosis (P = 0.018). There was no difference in survival between post-CML and non-post-CML patients with respiratory or GI malignancies.