Background: Children treated for cancer are at risk of developing iron toxicity due to receiving red cell transfusions and myelosuppressive chemotherapy. Transfusions administered during prolonged episodes of marrow suppression may increase exposure to toxic, reactive forms of iron and thereby increase risk of extrahepatic iron accumulation and long-term organ damage. Objective: This study aimed to evaluate the severity and organ distribution of clinically significant iron overload through measurement of hepatic, cardiac, pancreatic, and pituitary iron deposition in an at-risk cohort of children and young adults treated for cancer. Methods: This retrospective study evaluated patients treated for any type of cancer who underwent an MRI due to clinical concern for evaluation of iron overload (n=103, 73 post-treatment). Data regarding cancer type and treatment, MRI and laboratory results, and treatment for iron overload were analyzed. Results: Over half (53%) of this sample had moderate or greater hepatic siderosis, 80% had pancreatic siderosis, and nearly half (45%) had pituitary siderosis and/or volume loss. Pancreatic iron was associated with both cardiac (p=0.0043) and pituitary iron (p=0.0101). Patients treated for acute myeloid leukemia or high-risk acute lymphoblastic leukemia had higher liver iron concentration (LIC) compared to other cancer types (median LIC 8.5 vs. 2.9 mg/g DLW, p=0.0011). Conclusion: Pediatric cancer patients are at risk for transfusional iron overload, with significant exposure to toxic forms of iron indicated by extrahepatic iron deposition (pancreas, heart and pituitary). Further studies should examine the effect of exposure to reactive iron on long-term outcomes and develop management recommendations.