A new aptamer approach for the recognition of specific small cell lung cancer (SCLC) cell surface molecular markers relies on cell-based systematic evolution of ligands by exponential enrichment (cell-SELEX) to evolve aptamers for whole live cells that express a variety of surface markers representing molecular differences among cancer cells. When applied to different lung cancer cells including those from patient samples, these aptamers bind to SCLC cells with high affinity and specificity in different assay formats. When conjugated with magnetic and fluorescent nanoparticles, the aptamer nano-conjugates could effectively extract SCLC cells from mixed cell media for isolation, enrichment, and sensitive detection.