Fabricated Ag@Au core-shell nanoparticle (CS NP) assemblies exhibit pronounced and reverse chiral bisignate plasmonic signals spanning 400 to 580 nm, in comparison to Ag NP assemblies. The time-dependent chiro-optical response of assemblies that shift with shell deposition is systematically recorded. Chiral Ag@Au CS NP assemblies first achieve the special discrimination of circulating tumor cells with HER2 overexpression.