The discovery of novel protein biomarkers in melanoma is crucial. Our introduction of formalin-fixed paraffin embedded (FFPE) tumor protocol provides new opportunities to understand the progression of melanoma and open the possibility to screen tens of thousands of FFPE samples deposited in tumor biobanks and available at hospital pathology departments. In our retrospective pilot study, 90 FFPE samples from 77 patients were processed. Differential quantitative protein expression was performed by high resolution mass spectrometry. The protein expression profiles were correlated with the standardized dataset of histopathologic analysis, and longitudinal therapeutical meta-data.