Biomarkers are useful clinical tools but only a handful of them are used routinely for patient care. Despite intense efforts to discover new, clinically useful biomarkers, very few new circulating biomarkers were implemented in clinical practice in the last 40 years. This is mainly due to poor clinical performance. Here, our goal was to validate a group of newly discovered circulating biomarkers for glioma by comparing our data with data from a paper recently published in Science Advances. We analyzed our own sets of clinical samples and a different analytical assay to compare the results of Shen and colleagues. Despite the sophistication of the utilized discovery method, we found that the newly proposed biomarkers for glioma (such as SERPINA6) did not perform as expected. Scientific irreproducibility has been extensively discussed in the literature. A large proportion of newly discovered candidate biomarkers likely represent “false discovery” and contribute to irreproducible results. The best way to assess the value of any new biomarker is by independent and extensive validation. Based on our previous classification, we believe that this work represents another example of a false discovery.