Cell lines historically have been pivotal in advancing both basic and translational cancer research. For decades, scientists have attempted to develop bona fide models for growing and studying primary tumors outside of the human body. Even today, one of the greatest challenges in cancer biology research has been the development of a method to generate stable cancer cell lines from primary and metastatic tumors that can recapitulate the genotypic and phenotypic landscapes of the tumor of origin. Most primary cell cultures, regardless of the method used to generate them, suffer from limited lifespan due to a gradual decrease in proliferation rate eventually leading to cellular senescence. To address the current need of new models that can be robust, reliable and can keep the primary cells in culture for a long time without any genetic alterations, Schlegel’s group from Georgetown University described a method called “conditionally reprogramming” (CR) of cells. This CR technology uses mouse irradiated cells as feeder cells and ROCK inhibitor to grow patient’s epithelial cells from both normal and tumor tissue materials without any exogenous immortalization. However, before this rather novel CR cell model can be used for basic and translational research purposes it needed to be validated for genetic and phenotypic fidelity of the tumor of origin. This webinar is focused on the genomic tools that are being used to validate the CR technology for basic and translational research purposes.