In this paper, fluorescence metal nanoshells (FMNs) were synthesized for target molecule detection on tissue specimens by fluorescence imaging method. FMNs were made with 40 nm silica spherical cores and 10 nm silver shells. Ru(bpy)(3)(2+) complexes were encapsulated in the silica cores for fluorescence properties. Avidin molecules were covalently bound on FMNs and formed avidin-Ag complexes could be site-specially conjugated on bone tissue specimens. Fluorescence intensity and lifetime images were recorded on a time-resolved confocal microscope. Imaging measurements showed that the emissions by avidin-FMN complexes could be distinctly isolated as individuals from the cellular backgrounds on lifetime images even when the tissues were stained with additional organic dyes. This observation demonstrates that the metal nanoprobes can be used for single target molecule detection on tissues during fluorescence imaging measurements.