Cancer cells, after detaching from solid tumors migrate through the bloodstream to colonize at distant organs, leading to the development of cancer metastases. Cancer cells under circulation are called circulating tumor cells (CTCs). As blood-based bio-marker, CTCs offer the real-time snapshot of tumor evolution and therapeutic responses. Despite the promises, acute rareness of CTCs in blood hinders their isolation and characterization. The existing, marker-based sorting techniques fail to detect CTCs with atypical, non-epithelial phenotypes. Through a rigorous, data driven approach, we have come up with a panel of a few hundreds of genes that perfectly distinguishes between single cell transcriptomes of common blood cell types and CTCs.