Patients approach genetic testing, either for germline (inherited) or somatic (tumor) alterations, hoping it will provide valuable information about their cancer risk, prognosis, or treatment options. Next-generation sequencing (NGS) makes it possible to test for panels of 40 or more genes simultaneously. By testing more genes, the possibility of finding an actionable, informative result improves, but so does the chance of having a result with one or more variants of unknown clinical significance (VUS).