In conclusion, the results reported in the present study, starting from a new methodological approach, represent: a) the first evidence that serum contains a large amount of protein information, currently underestimated according to a single denaturation step, indicating a novel strategy for further biomarkers discovery based on the comparison of differentially denatured samples; b) the first in vivo evidence about a possible role of α2MG, Apo E and Apo A1 as early diagnostic predictors in cutaneous melanoma patients to be further investigated. The gene discussed is APOE; the disease is cutaneous melanoma.