Tungsten carbide (WC) and cobalt (Co) are constituents of hard metals and are used for the production of extremely hard tools. Previous studies have identified greater cytotoxic potential of WC-based nanoparticles if particles contained Co. The aim of this study was to investigate whether the formation of reactive oxygen species (ROS) and micronuclei would help explain the impact on cultured mammalian cells by three different tungsten-based nanoparticles (WC_S, WC_L, WC_L–Co (S: small; L: large)). The selection of particles allowed us to study the influence of particle properties, e.g. surface area, and the presence of Co on the toxicological results. WC_S and WC_L/WC_L–Co differed in their crystalline structure and surface area, whereas WC_S/WC_L and WC_L–Co differed in their cobalt content. WC_L and WC_L–Co showed neither a genotoxic potential nor ROS induction. Contrary to that, WC_S nanoparticles induced the formation of both ROS and micronuclei. CoCl₂ was tested in relevant concentrations and induced no ROS formation, but increased the rate of micronuclei at concentrations exceeding those present in WC_L–Co. In conclusion, ROS and micronuclei formation could not be associated with the presence of Co in the WC-based particles. The contrasting responses elicited by WC_S vs. WC_L appear to be due to large differences in crystalline structure.