An increasing percentage of the population is getting genetic testing as a diagnostic test based on symptoms, or as a risk assessment through population screening, or due to family history of a known or suspected genetic disease. As the indications for testing and the number of genes tested expand, so does the potential for variants of uncertain significance (VUSs) to be detected and returned to individuals. Additionally, the prevalence of VUSs are disproportionately higher in underrepresented minority populations due to both the paucity of literature in affected individuals from these populations and a lack of representation in databases. To date, most laboratories do not report VUSs in the context of population screening but do report VUSs for diagnostic testing given the potential to follow-up. This includes resolving VUSs if other family members are available for segregation studies, using clinical tests to inform a VUS, or waiting for additional data that may be generated over time. However, there are increasingly blurry lines between these testing paradigms and a need to engage the community in dialogue around when it is appropriate to return a VUS, when returning a VUS may do more harm than good, and how to guide clinical laboratory practices that are not labor intensive. For example, should a healthy individual seeking cancer risk screening have VUSs returned in their report? Some say no, others say yes, others feel it is context dependent. If an unaffected individual is part of a large family with many individuals segregating features of an inherited cancer syndrome, and follow-up segregation testing could be informative, then some would argue yes. For another unaffected individual whose family has no clear features of a condition and all affected family members are deceased, the utility of returning a VUS may be minimal and the potential for harm higher. Furthermore, not all VUSs are created equal and up to 90% of VUSs are eventually downgraded to Likely Benign. Some VUSs have substantial evidence towards pathogenicity but fall slightly below the line for classification as Likely Pathogenic. Yet the majority of VUSs have no evidence, some being found in population databases but at a frequency that is not quite sufficient to classify as Likely Benign. Should there be policies that distinguish these types of VUSs; should policies for return of VUS results incorporate these subcategories; and should laboratories be expected to subcategorize VUSs?