Melanoma is one of the most aggressive skin cancers. The 5-year survival rate of stage III melanoma patients ranges from 93% (IIIA) to 32% (IIID) with a high risk of recurrence after complete surgery. The introduction of target and immune-therapies has dramatically improved the overall survival, but it remains crucial to identify patients with a high risk of relapse who will benefit from adjuvant therapy and to determine the best treatment choice. The project aims to identify novel biomarkers (prognostic and/or predictive), through the analysis by Next-Generation Sequencing of stage III/IV NED melanoma samples. The first step of the project will be the characterization of primary melanoma tumour, using the Illumina TSO500 panel. The panel is able to evaluate more than 500 genes involved in tumorigenesis, immunity and microenvironment. Next, we will study liquid biopsies of patients treated in adjuvant therapy, with the aim to follow the disease over time and predict the risk of relapse/progression.