IRMM-304 is a new nanoparticle reference material (RM) consisting of silica nanoparticles suspended in an aqueous solution, of which the particle size was characterized by dynamic light scattering (DLS) and centrifugal liquid sedimentation (CLS). The homogeneity and stability of IRMM-304 were confirmed and three method-specific mean particle sizes around a nominal particle size of 40 nm were assigned to the material. The characterization tests have revealed a systematic deviation between the measurement results obtained with DLS and CLS. The availability of IRMM-304 makes it possible to study this difference between methods. Several possible causes for differences between the DLS and CLS results are suggested and preliminarily investigated, such as the interaction between particle and suspending medium, the particle shape and the effect of polydispersity on the size averaging procedure. These investigations are one illustration of the potential role of IRMM-304 and other nanoparticle RMs in the development, comparison, improved understanding, and quality assurance of nanoparticle sizing methods.