Natasha Leighl, MD, MMSc, FRCPC, Princess Margaret Cancer Center, Ontario, Canada, discusses how to balance next generation sequencing in tissue biopsy vs liquid biopsy in clinical practice, focusing on lung cancer. The use of effective molecular testing can lead to better use of targeted therapies, especially when a large range of genomic markers are tested for. Minimally-invasive tissue biopsies of lung cancer tumors result in small samples, which can pose problems for carrying out molecular testing. A further challenge for next generation sequencing is improving access to it. Prof. Leighl also compares the cost-effectiveness of tissue biopsies vs liquid biopsies and their most-likely subsequent treatment regimens. This interview took place at the International Society of Liquid Biopsy (ISLB) 2021 Virtual Meeting.