<b>Conclusions:</b> While <i>NRAS</i> and <i>BRAF</i> were the most frequent actionable alterations (each 25%), a broad spectrum of variants of unknown significance (e.g., <i>FANDC2</i>, <i>NOTCH3</i>, <i>ARID1A</i>, <i>PMS2</i>, <i>POLE</i>, <i>NOTCH1</i>, <i>TSC2</i>, <i>SMARCA4</i>, <i>ATR</i> and <i>TERT</i>) also predominates, underscoring the genetic complexity of melanoma. This evidence concerns the gene NOTCH3 and melanoma.