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Despite its successful use in academic research, next-generation sequencing (NGS) still represents many challenges for routine clinical adoption due to its inherent complexity and specialised expertise typically required to set-up, test and operate a complete workflow.This study aims to evaluate QIAGEN's newly launched GeneReader NGS System solution in a pathology laboratory setting by assessing the system's ease of use, sequencing accuracy and data reproducibility. Our laboratory was able to implement the system and validate its performance using clinical samples in direct comparison to an approved Sanger sequencing platform and to an alternative in-house NGS technology. The QIAGEN workflow focuses on clinically actionable hotspots maximising testing efficiency. Combined with automated upstream sample processing and integrated downstream bioinformatics, it offers a realistic solution for pathology laboratories with limited prior experience in NGS technology.