The in vitro cytotoxicity and cellular uptake of commercially available doped YVO4 were evaluated in RAW 264.7 macrophages using the MTT assay. The results indicated that 20–50 nm diameter samarium-doped YVO4 showed significant toxicity at concentrations of 25 μg/mL and higher; samples of the same material functionalized with COOH showed less cytotoxicity. At concentrations of 25–100 μg/mL, 20–50 nm erbium-doped YVO4 showed less toxicity compared with 20–50 nm samarium-doped YVO4. Ten nanometer samples showed no toxicity at concentrations of 100–600 μg/mL. The cytotoxicity of rare earth nanoparticles in macrophages is dependent, at least in part, on size and surface functionalization.