Recurrence of glioblastoma (GBM) can be localized in situ or at distant sites, but the two different recurrence patterns have been less studied, making it more difficult to talk about the issue of treatment strategies. Kim J et al. of Samsung Biomedical Center, Seoul National University, Korea, published in the September 2015 issue of Cancer Cell the results of a study on the spatio-temporal changes in genomics occurring during recurrence of primary glioblastoma, and found that GBM recurring at distant compartment sites is characterized completely differently from primary tumors. The study collected primary and recurrent paired tumor specimens from 23 GBM patients for genomic analysis. Subsequent bioinformatic analysis of genomic changes in GBM with distant site recurrence and local recurrence in situ revealed that GBM with distant site recurrence had novel driver gene alterations. In contrast, the genomics of GBM with local recurrence in situ is similar to that of primary tumors, and appropriate targeted therapies can be selected based on the genomic features of primary tumors. Genomic differences in recurrent gliomas. A. Relationship between recurrence site and mutation rate; B. Proportion of common versus specific mutations between recurrent and primary tumors. To further investigate the spatiotemporal evolution of GBM recurrence, the authors analyzed the microevolutionary features of the genomics of primary and recurrent paired tumor specimens from four patients. The evolutionary tree diagram showed that recurrent tumors at distant sites had more abnormal driver gene alterations than locally recurrent tumors in situ. Also, IDH1 wild-type primary GBM was less likely to have post-TMZ treatment hypermutations compared to IDH1 mutant GBM. The spatiotemporal evolution of primary and recurrent tumors in patients with case 2 and case 9 was plotted, with dynamic changes in imaging associated with driver gene alterations. This study suggests that IDH1 wild-type primary GBM has a low probability of hypermutation after standardized treatment, and this result is an important guide for the clinical management of IDH1 wild-type GBM with local recurrence in situ. In addition, GBM with distant site recurrence has different driver gene alterations from primary tumors, thus emphasizing the importance of re-biopsy for GBM with distant site recurrence.