The plurality of clonogenic cells derived from human lung includes a spectrum of diverse p63+ stem cells responsible for the regeneration of normal epithelial tissue and disease-associated metaplastic lesions. Here, we report protocols for the cloning, expansion, and characterization of these stem cell variants, which in general assist in analyses of stem cell heterogeneity, genome editing, drug screening, and regenerative medicine. For complete details on the use and execution of this protocol, please refer to Kumar et al. (2011), Zuo et al. (2015), and Rao et al. (2020).