When it comes to glioblastoma, the ability to noninvasively diagnose the disease, assess its prognosis, and foretell its clinical outcomes, the liquid biopsy platform is appealing. Previous research has shown that the EGFRvIII mutation is present in 30%-50% of EGFR-amplified GBM tumors. For the sensitive detection of EGFRvIII in glioma tumor tissue and in circulating extracellular vesicle RNA (EV RNA) isolated from plasma, a novel digital droplet PCR (ddPCR) test for high GC content amplicons was designed and improved. In 81% [95% CI, 68%-94%] of EGFR-amplified glioma tumor tissue, researchers found EGFRvIII mRNA, suggesting a higher incidence of EGFRvIII in glioblastoma than has been previously described. With the improved ddPCR test, they found EGFRvIII mutation in 73% (95% CI, 64%-82%) of patients as compared with qPCR tumor tissue analysis, with a sensitivity of 98% (95% CI, 87%-100%). Furthermore, they reported the discovery of EGFRvIII in the plasma of patients with varying clinical outcomes, with levels increasing with tumor growth and decreasing in response to treatment. This was based on longitudinal surveillance of 4 patients. In this study, they showed that a highly sensitive and specific ddPCR test may be used to identify EGFRvIII mutation in plasma. They also demonstrated an increased EGFRvIII prevalence in glioma tumor tissue compared to prior reports. The assay has several properties that make it well-suited for clinical use in the diagnosis and follow-up of EGFRvIII-positive malignancies.