In this paper, we investigate the performance of a piezoelectric membrane actuated by an epitaxial piezoelectric Pb(Zr0.2Ti0.8)O-3 (PZT) thin film for localized-mass sensing applications. The fabrication and characterization of piezoelectric circular membranes based on epitaxial thin films prepared on a silicon wafer are presented. The dynamic behavior and mass sensing performance of the proposed structure are experimentally investigated and compared to numerical analyses. A 1500 mu m diameter silicon membrane actuated by a 150 nm thick epitaxial PZT film exhibits a strong harmonic oscillation response with a high quality factor of 110-144 depending on the resonant mode at atmospheric pressure. Different aspects related to the effect of the mass position and of the resonant mode on the mass sensitivity as well as the minimum detectable mass are evaluated. The operation of the epitaxial PZT membrane as a mass sensor is determined by loading polystyrene microspheres. The mass sensitivity is a function of the mass position, which is the highest at the antinodal points. The epitaxial PZT membrane exhibits a mass sensitivity in the order of 10(-12) g/Hz with a minimum detectable mass of 5 ng. The results reveal that the mass sensor realized with the epitaxial PZT thin film, which is capable of generating a high actuating force, is a promising candidate for the development of high performance mass sensors. Such devices can be applied for various biological and chemical sensing applications.