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Objective: In this review, we evaluate the role of liquid biopsy in managing lung cancer patients during the still ongoing coronavirus disease 2019 (COVID-19) healthcare emergency., Background: The novel influenza coronavirus (severe acute respiratory syndrome coronavirus or SARS-CoV-2) has upended several aspects of our lives, including medical activities. In this setting, many routine cancer diagnostic and therapeutic procedures have been suspended, leading to delays in diagnosis, treatments, and, ultimately, increases in cancer mortality rates. Equally drastic has been the impact of COVID-19 on clinical trials, many of which have been stalled or have never begun. This has left many patients who were hoping to receive innovative treatments in a limbo. Although, as of today, the introduction of drastic security measures has been crucially important to contain the pandemic, one cannot ignore the need to continue providing chronically ill patients all the health care they need, in terms of detection, prevention, and treatment. In these unprecedented times, liquid biopsy, more than ever before, may play a relevant role in the adequate management of these frail patients., Methods: we performed a deep analysis of the recent international literature published in English on PUBMED in the last six months focused on the impact of SARS-CoV-2 on the management of lung cancer patients, focusing the attention on the role of liquid biopsy., Conclusions: COVID-19 pandemic has significantly modified our lives and overall medical practice. In these unprecedented times, liquid biopsy may represent a valid and less time-consuming diagnostic approach than conventional tissue and cytological specimens., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at: https://dx.doi.org/10.21037/med-21-9). The series “Changes in management of mediastinal tumours following the surge of COVID-19 pandemic” was commissioned by the editorial office without any funding or sponsorship. The authors have no other conflicts of interest to declare., (2021 Mediastinum. All rights reserved.)