Proteomics of invasiveness opens a window on the complexity of the metastasis-engaged mechanisms. The extend and types of this complexity require elucidation. Proteomics, immunohistochemistry, immunoblotting, network analysis and systems cancer biology were used to analyse acquisition of invasiveness by human breast adenocarcinoma cells. We report here that invasiveness network highlighted the involvement of hallmarks such as cell proliferation, migration, cell death, genome stability, immune system regulation and metabolism. Identified involvement of cell-virus interaction and gene silencing are potentially novel cancer mechanisms. Identified 6,113 nodes with 11,055 edges affecting 1,085 biological processes show extensive re-arrangements in cell physiology. These high numbers are in line with a similar broadness of networks built with diagnostic signatures approved for clinical use. Our data emphasize a broad systemic regulation of invasiveness, and describe the network of this regulation. Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.