This study leverages single-cell RNA-seq to investigate the intratumoral heterogeneity in primary glioblastomas. The authors isolated and profiled 430 cells from five primary glioblastoma tumors, revealing a wide range of transcriptional programs related to oncogenic signaling, proliferation, complement/immune response, and hypoxia. They identified a continuum of stemness-related expression states, suggesting the presence of putative regulators of stemness in vivo. The study also found that established glioblastoma subtype classifiers are variably expressed across individual cells within a tumor, highlighting the potential prognostic implications of such intratumoral heterogeneity. These findings underscore the complexity of glioblastoma biology and the need for more nuanced therapeutic strategies that account for the diverse cellular states within tumors.This study leverages single-cell RNA-seq to investigate the intratumoral heterogeneity in primary glioblastomas. The authors isolated and profiled 430 cells from five primary glioblastoma tumors, revealing a wide range of transcriptional programs related to oncogenic signaling, proliferation, complement/immune response, and hypoxia. They identified a continuum of stemness-related expression states, suggesting the presence of putative regulators of stemness in vivo. The study also found that established glioblastoma subtype classifiers are variably expressed across individual cells within a tumor, highlighting the potential prognostic implications of such intratumoral heterogeneity. These findings underscore the complexity of glioblastoma biology and the need for more nuanced therapeutic strategies that account for the diverse cellular states within tumors.