Pediatric cancer patients are at increased risk of subsequent malignant neoplasms (SMNs). However, little is known about the contribution of hematopoietic SCT (HSCT) to the development of SMNs. The objective of this study was to compare the incidence of SMNs in a population cohort of childhood cancer survivors treated with and without HSCT. A cohort of 7986 children (age 0-14 years) diagnosed with cancer in the province of Ontario, Canada between 1985 and 2009 was identified in POGONIS (Pediatric Oncology Group of Ontario Networked Information System), a population-based active cancer registry, and linked to a clinical HSCT database. Among this cohort, 796 patients had an HSCT as part of their primary treatment. Of the 375 allogeneic HSCT patients, 14 (3.7%) developed a SMN at a median follow-up of 12.3 years (range: 2.0-22.9 years). Of the 421 autologous HSCT patients, 8 (1.9%) developed a SMN at a median of 4.5 years (range: 1.3-14.3 years). Of the 7190 patients who did not receive an HSCT, 160 (2.2%) developed a SMN at a median follow-up of 6.8 years (range: 0.0-24.9 years). The 15-year cumulative incidence of SMN was 3.1% among the allogeneic HSCT group, 2.5% among the autologous group and 2.3% in the non-HSCT group. The cumulative incidence curves for the allogeneic HSCT and non-transplant groups only diverged after ˜ 15 years from primary diagnosis. Our findings further corroborate the observation that children who undergo allogeneic HSCT are at a significantly increased risk of developing SMN compared with pediatric cancer survivors treated without HSCT.