A Mayo Clinic review in the Journal of Neuro-Oncology lays out why MGMT promoter methylation remains pivotal for brain tumor treatment selection—but also why testing methods still disagree. The piece summarizes sources of variability across assay platforms, pre-analytical handling, and interpretation. For clinicians, the practical implication is that a biomarker’s clinical utility depends on consistent measurement and quality control, not only on biological relevance. The review also surveys emerging technologies aimed at harmonizing testing and improving inter-lab concordance. As molecular stratification becomes more central in neuro-oncology, the field’s near-term focus is on reducing discordant results that can translate into mismatched treatment decisions for patients.