The term Cancer Stem Cells (CSCs) has been coined to refer to a subpopulation of tumor cells that has the ability to self-renew and to generate the diverse cell pool of a given tumor. In the last decade CSCs have been receiving a lot of interest due to their cancer initiating and maintaining capabilities making them the real driving force within a malignant mass that pushes towards more aggressive proliferation and more resistance against anticancer drugs. These cells have been linked to different specific markers in an attempt to achieve efficient isolation and characterization. Such markers include CD44, EpCAM and CD133 among others. Aptamers are synthetic single stranded oligonucleotides selected from a huge pool of random sequences which can fold and bind to a wide range of targets with high affinity and specificity. They are not immunogenic or toxic and have good clearance rates, qualities that make aptamers a good rival to monoclonal antibodies in their diagnostic as well as therapeutic applications.