Uniform Y2O3 hollow microspheres have been successfully prepared via a urea-based homogeneous precipitation technique with colloidal melamine formaldehyde (MF) microspheres as templates followed by a subsequent calcination process. X-ray diffraction, energy dispersive X-ray analysis, and Fourier transform infrared spectroscopy results show that the MF templates can be effectively removed, and the amorphous precursor has converted to crystalline Y2O3 during the annealing process. Scanning electron microscopy and transmission electron microscopy images indicate that the Y2O3 hollow spheres inherit a spherical shape and good dispersion of MF templates, and the shell of the hollow spheres is composed of a large amount of uniform nanoparticles. The lanthanide activator ion Ln(3+)-doped Y2O3 hollow microspheres exhibit bright down- and upconversion luminescence with different colors coming from different activator ions under ultraviolet or 980 nm light excitation, which may find potential applications in fields such as light phosphor powders, advanced flat panel displays, or drug delivery.