Perturbation in iron homeostasis is a hallmark of some hematologic diseases. Abnormal sideroblasts with accumulation of iron in the mitochondria are named ring sideroblasts (RS). RS is a cardinal feature of refractory anemia with RS (RARS) and RARS with marked thrombocytosis (RARS/-T). Mutations in SF3B1, a member of the RNA-splicing are frequent in RARS/-T and defects of this gene were linked to RS formation. Here we showcase the differences in iron architecture of SF3B1 mutant and wild type (WT) RARS/-T and provide new mechanistic insights by which SF3B1 mutations lead to differences in iron. We found higher iron levels in SF3B1 mutant vs WT RARS/-T by transmission electron microscopy/spectroscopy/flow cytometry. SF3B1 mutations led to increased iron without changing the valence as shown by the presence of Fe2+ in mutant and WT. Reactive-oxygen-species and DNA-damage were not increased in SF3B1 mutant patients. RNA-Seq and RT-PCR showed higher expression of a specific isoform of SLC25A37 in SF3B1 mutant patients, a crucial importer of Fe2+ into the mitochondria. Our studies suggest that SF3B1 mutations contribute to cellular iron overload in RARS/-T by deregulating SLC25A37.Leukemia accepted article preview online, 23 May 2014; doi:10.1038/leu.2014.170.