People who have a particular genetic variant in their MITF gene, known as p.E318K, are at increased risk of developing melanoma. The scientific community continues to debate whether this variant also increases the risk of developing renal cell carcinoma (RCC). This manuscript advances this debate by bringing together previous research reports with new research findings. We find that further evidence is still required to determine if this variant increases the risk of developing RCC. It remains imperative to resolve this issue so that information about this variant can be used clinically to support genetic counselling and cancer risk management. (By Dr Philip Harraka, https://jmg.bmj.com/content/early/2024/08/01/jmg-2024-109984 )