Background: We have developed a method, termed laser-activated nano-thermolysis as a cell elimination technology (LANTCET), for the selective detection and destruction of individual tumor cells by the generation of intracellular photothermal bubbles around clusters of gold nanoparticles. Method: Bare nanoparticles and their conjugates to C225 tumor-specific monoclonal antibodies were applied in vitro to C225-positive squamous carcinoma cells and in vivo to an experimental tumor in a rat in order to form intracellular clusters of nanoparticles. Results: Single 10 ns laser pulses generated intracellular photothermal microbubbles at a near-infrared and visible wavelengths. The cells with the clusters yielded an almost 100-fold decrease in the laser fluence threshold for bubble generation and cell damage relative to that for the cells without clusters. Cell damage had a mechanical origin and single cell selectivity. Three LANTCET processes (cell detection, damage and optical guidance) were realized as a microsecond sequence and with the one device.