Abstract Elevated levels of circulating ferritin have been associated with several neoplasms, including neuroblastoma, glioblastoma, Hodgkin's lymphoma, and breast cancer. Despite the prognostic value of serum ferritin levels, its role in cancer biology is not understood. Ferritin has long been considered exclusively as an intracellular iron storage protein. However, several lines of evidence have suggested a role for ferritin beyond iron storage, such as angiogenesis, iron delivery, and modulation of the immune response. Recently, a receptor for L-ferritin (the predominant ferritin subunit in the serum and cerebrospinal fluid) has been identified as scavenger receptor class A, member 5 (Scara5). Our preliminary data show Scara5 to be expressed in glioma, neuroblastoma, and breast cancer cells. This novel observation led us to hypothesize that Scara5 internalizes L-ferritin, and serves as a non-transferrin iron delivery mechanism in cancer cells. In support of this hypothesis, we report here that both human liver and human heart ferritins increased cellular survival of the breast cancer cell line MCF-7 in serum free conditions. Taken together, these observations suggest an active functional role for circulating ferritin in tumor biology. The elevated levels of circulating ferritin observed in some cancers may enhance tumor metabolism and growth. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 84.