Next generation sequencing for liquid biopsy based testing in non-small cell lung cancer in 2021

•Lung cancer is the leading cause of cancer death worldwide.•A considerable fraction of advanced NSCLC patient presents tissue unavailability for molecular analysis.•In this context, liquid biopsy is on the rise.•NGS biology methodologies is a rapidly evolving field for liquid biopsy. Lung cancer is the leading cause of cancer death worldwide, with non-small cell lung cancer (NSCLC) representing its most commonly diagnosed sub-type. Despite the significant improvements in lung cancer biomarkers knowledge, accompanied by substantial technological advances in molecular tumor profiling, a considerable fraction (up to 30 %) of advanced NSCLC patient presents with major testing challenges or tissue unavailability for molecular analysis. In this context, liquid biopsy is on the rise, currently gaining considerable interest within the molecular pathology and oncology community. Molecular profiling of liquid biopsy specimens using next generation molecular biology methodologies is a rapidly evolving field with promising applications not exclusively limited to advanced stages but also more recently expanding to early stages cancer patients. Here, we offer an overview of some of the most consolidated and emerging applications of next generation sequencing technologies for liquid biopsy testing in NSCLC.