Genome-wide association studies (GWAS) have identified associations between common genetic variants, single nucleotide polymorphisms (SNPs) and the risk of developing different cancers1,2,3. Proponents argue that polygenic risk score (PRS) testing, based on panels of risk SNPs, will revolutionize the prevention and early detection of cancer through individualised risk management strategies and streamlining of the current ‘one-size-fits all’ population screening programs4. Such a model is highly seductive for the rationalisation of healthcare provision. UK government enthusiasm for PRSs is well demonstrated within the recent Genome UK report and 2020 update to the Life Sciences Strategy5. Indeed, reflecting governmental endorsement of predictive genomics, the UK government’s Secretary of State for Health and Social Care, Matthew Hancock, rather questionably enthused that his recent PRS-derived lifetime prostate cancer risk estimate of 15% (compared to a prior of 13%) “may have saved his life”6,7. To establish the requisite governance and data infrastructure for population-level genomic profiling, national projects such as the 100,000 Genomes Project (>70,000 NHS patients) and the Accelerating Detection of Disease programme (up to 5 million volunteers) were initiated8,9. Following initial discontinuation by the U.S. Food and Drug Administration of the 23andMe PRS service10,11, there has been a resurgence within the direct-to-consumer genomics market of PRS predictions for many diseases. While the value of additional biomarkers to improve the targeting of measures for cancer prevention and early detection is indisputable, for PRS to be clinically useful, two assertions must be proven correct. The first assertion is that PRSs provides sufficient risk discrimination. The second is that this risk discrimination is meaningful in the context of absolute risk of that cancer and applicable in the context of respective tools available for prevention and early detection.