: With the integration of various targeted therapies into the clinical management of patients with advanced lung adenocarcinoma, next-generation sequencing (NGS) has become the technology of choice and has led to an increase in simultaneously interrogated genes. However, the broader adoption of NGS for routine clinical practice is still hampered by sophisticated workflows, complex bioinformatics analysis and medical interpretation. Therefore, the performance of the novel QIAGEN GeneReader NGS system was compared to an in-house ISO-15189 certified Ion PGM NGS platform. : Clinical samples from 90 patients (60 Retrospectively and 30 Prospectively) with lung adenocarcinoma were sequenced with both systems. Mutations were analyzed and , , , , , and genes were compared and sampling time and suitability for clinical testing were assessed. : Both sequencing systems showed perfect concordance for the overlapping genes. Correlation of allele frequency was ² = 0.93 for the retrospective patients and ² = 0.81 for the prospective patients. Hands-on time and total run time were shorter using the PGM system, while the GeneReader platform provided good traceability and up-to-date interpretation of the results. : We demonstrated the suitability of the GeneReader NGS system in routine practice in a clinical pathology laboratory setting.