In the advanced stages, malignant melanoma (MM) has a very poor prognosis. Due to tremendous efforts in cancer research, the overall survival of metastatic melanoma has doubled; however, complete eradication of the disease is almost unknown. With the advent of proteomics, deep-mining studies can reach low-abundant expression areas. The complexity of the proteome, however, still surpasses the dynamic range capabilities of current analytical techniques. Consequently, many predicted protein products with potential biological functions have not yet been verified in experimental proteomic data. This category of ‘missing proteins’ (MP) is comprised of all proteins that have been predicted but are currently unverified. As part of the initiative launched in 2016 in the United States, the European Cancer Moonshot Center has performed numerous deep proteomics analyses on samples from MM patients. In this study, nine MPs were clearly identified by mass spectrometry in MM metastases. Some MPs significantly-correlated with proteins that possess identical PFAM structural domains; and other MPs were significantly-associated with cancer-related proteins. This is the first study to our knowledge, where unknown and novel proteins have been annotated within metastasis, from Melanoma Cancer patients.