The detection and characterization of circulating tumor cells (CTC) in serum holds great promise for early diagnoses and optimized systemic therapy.However, low specificity, low sensitivity, and the time consuming nature of current approacbes have impeded clinical adoption.Herein we report a new method using surface enhanced Raman scattering(SERS) to detect sinlge targeted CTC directly in the glass substrate.SERS nanoptags are created by coating 60-nm gold nanoparticles with Raman reporter molecules and antibodies EpCam-CD326 specific for the target CTC.4-mercaptobenzoic acid(MBA) self-assembled on the surface of gold nanopartieles functions as raman reporter molecule and link covalently binding antibodies to the gold particles.We have detected the single CTC of non-small lung cancer NCI-H1650 successfully in patient serum.Our technique may provide an important new clinical tool for management of lung cancer patients and other cancers.