Biocompatible and green luminescent monodisperse silver/phenol formaldehyde resin core/shell spheres with controllable sizes, in the range of 180 to 1000 nm, and interesting architectures (centric, eccentric, and coenocytic core/shell spheres) have been synthesized by a facile one-step hydrothermal approach. These spheres can be used as bioimaging labels for human lung cancer H1299 cells. The results demonstrate that the nanoparticles can be internalized into cells and exhibit no cytotoxic effects, showing that such novel biocompatible core/shell structures can potentially be used as in vivo bioimaging labels. This facile one-pot polymerization and encapsulation technique may provide a useful tool to synthesize other core/shell particles that have potential application in biotechnology.