Molecular stratification of melanoma based on NRAS and BRAF has been useful to apply especially for targeted therapies. However, these patients have a resistance to this treatment and the clinical benefit is limited. Most recently molecular characterisation based on NGS sequencing has revealed that there are distinct subsets of melanoma, in addition that melanoma has a high burden of mutation. This information can be useful to detect those melanoma patients that respond to immunotherapy and, in addition, analysis of molecular alterations such as BRAF mutations in circulating free DNA from blood can help us to detect and to monitor the signs of a treatment response. In order to achieve a good personalised medicine in melanoma it is necessary to apply these kinds of molecular genomic strategies.