Silver (Ag) nanoparticles have unique plasmon-resonant optical scattering properties that are finding use in nanomedical applications such as signal enhancers, optical sensors, and biomarkers. In this study, we examined the chemical and biological properties of Ag nanoparticles of similar sizes, but that differed primarily in their surface chemistry (hydrocarbon versus polysaccharide), in neuroblastoma cells for their potential use as biological labels. We observed strong optical labeling of the cells in a high illumination light microscopy system after 24 h of incubation due to the excitation of plasmon resonance by both types of Ag nanoparticle. Surface binding of both types of Ag nanoparticle to the plasma membrane of the cells was verified with scanning electron microscopy as well as the internalization and localization of the Ag nanoparticles into intracellular vacuoles in thin cell sections with transmission electron microscopy. However, the induction of reactive oxygen species (ROS), degradation of mitochondrial membrane integrity, disruption of the actin cytoskeleton, and reduction in proliferation after stimulation with nerve growth factor were found after incubation with Ag nanoparticles at concentrations of 25 µg ml⁻¹ or greater, with a more pronounced effect produced by the hydrocarbon-based Ag nanoparticles in most cases. Therefore, the use of Ag nanoparticles as potential biological labels, even if the surface is chemically modified with a biocompatible material, should be approached with caution.