Iron plays a central role in cellular redox processes, but its ability to adopt multiple oxidation states also enables it to catalyze deleterious reactions. The requirement for iron in erythropoiesis has necessitated the evolution of mechanisms with which to handle the iron required for hemoglobinization. FAM210B was identified as a regulator of mitochondrial iron import and heme synthesis in erythroid cell culture and zebrafish models. In this manuscript, we demonstrate that while FAM210B is required for erythroid differentiation and heme synthesis under standard cell culture conditions, holotransferrin supplementation was sufficient to chemically complement the iron-deficient phenotype. As the biology of FAM210B is complex and context specific, and whole-organism studies on FAM210 proteins have been limited, we sought to unravel the role of FAM210B in erythropoiesis using knockout mice. We were surprised to discover that Fam210b -/- mice were viable and the adults did not have erythropoietic defects in the bone marrow. In contrast to studies in C. elegans, Fam210b -/- mice were also fertile. There were some modest phenotypes, such as a slight increase in lymphocytes and white cell count in Fam210b -/- females, as well as an increase in body weight in Fam210b -/- males. However, our findings suggest that FAM210B may play a more important role in cellular iron homeostasis under iron deficient conditions. Here, we will discuss the cell culture conditions used in iron metabolism studies that can account for the disparate finding on FAM210B function. Moving forward, resolving these discrepancies will be important in identifying novel iron homeostasis genes.