Glioblastoma (GBM) is the most aggressive, and most common, malignant primary brain tumor. We are mapping intra-tumor heterogeneity, via high-throughput single-cell sequencing of matched cohorts of primary and recurrent GBMs. Our goal is to assess the mechanisms with which subclones from primary GBMs evade treatment, and populate secondary tumors. Via a clonal ordering of individual cells, we are constructing high-resolution phylogenies to model tumor evolution. This provides a window into the history of the tumor’s origin, growth process and response to treatment.