Updated project metadata. The proteomics analysis of circulating exosomes derived from cancer cells represents a promising approach to the elucidation of cell-cell communication and the discovery of putative biomarker candidates for cancer diagnosis and treatment. Nonetheless, the proteome of exosomes derived from cell lines with different metastatic capabilities still warrants further investigation. Here, we present a comprehensive quantitative proteomics investigation of exosomes isolated from im-mortalized mammary epithelial cells and matched tumor lines with different metastatic potential, in an attempt to discover exosome markers specific to breast cancer (BC) metastasis. A total of 2,135 unique proteins were quantified with a high confidence level from 20 isolated exosome samples, including 94 of the TOP 100 exosome markers archived by ExoCarta, e.g., CD9, HSPa8, and PDCD6IP. Moreover, 344 altered proteins were observed, among which several metastasis-specific markers, including CATW, MRS2, SDCB2, RTN4, and RAD23B, were also identified. Notably, the abundance of these metastasis-specific corresponds well with the overall survival of BC patients in clinical settings. Together, these data provide a valuable dataset for BC exosome proteomics in-vestigation and prominently facilitate the elucidation of the molecular mechanisms underlying primary tumor development and progression.