ERBB2 and cancer: To capitalize on the wealth of information that can be generated through mass spectrometric analysis, this study was aimed at characterizing the cell-surface proteome of SKBR3/HER2+ breast cancer cells by using orthogonal methods for cell-surface protein enrichment and isolation, categorizing these proteins based on their functional role and relevance to cancer, identifying key drivers of aberrant proliferation, and exploring the opportunities presented by such cells for the development of effective diagnostic and therapeutic approaches.