Our preliminary results show that by jointly considering the panel of biomarkers here investigated the highest predictive capability is given by total cfDNA followed by integrity index 180/67 and methylated RASSF1A. According to these results, an approach based on the simultaneous determination of the three biomarkers (total cfDNA, integrity index 180/67 and methylated RASSF1A) could be suggested to improve the diagnostic performance in melanoma. The gene discussed is RASSF1; the disease is melanoma.