In this study, we explore the role of intrinsically disordered proteins (IDPs) in human breast cancer within the context of the "unfoldome." Using advanced proteomic techniques, we identified 2,271 protein groups in both normal and cancerous cell proteomes. Notably, 148 IDPs displayed significant differential expression in cancer cells, with a particular focus on cancer-related proteins. In our functional annotation, we found that 65% of these IDPs were linked to various diseases, with 20% specifically associated with cancer. Moreover, a substantial portion of the differentially expressed IDPs contained disordered regions, as verified through in silico characterization. By classifying IDPs into major Gene Ontology categories and conducting pathway analysis, our results highlight a high degree of interactivity within the altered portion of the human unfoldome in cancer, emphasizing the prevalence of moderately and highly disordered proteins in these networks. This study further elucidates the pivotal role of IDPs in the molecular mechanisms of breast cancer.