With the increasing interest in nanoparticles (NPs), various ways of detecting and measuring them are being used. One of the most promising techniques for analyzing metallic NPs is single particle ICP-MS (SP-ICP-MS). This work demonstrates the ability of the NexION® SP-ICP-MS with Universal Cell Technology to measure iron (Fe) NPs in Reaction mode. Because iron suffers from plasma-based interferences, the use of Reaction mode is necessary to detect Fe nanoparticles and provides significant benefits over Collision mode.