In order to preliminarily explore any correlation between surface and released NKG2D-L for liquid biopsy, EV-MICA was analysed for the first time in parallel to soluble MICA, MICB and ULBP2 in sera from 29 melanoma patients, obtained at different time points after beginning the treatment with BRAFi, MEKi, combined targeted therapies or placebo in a clinical trial. This evidence concerns the gene ULBP2 and melanoma.