In the present study, total proteins from a tissue of an infiltrating ductal carcinoma of the breast (IDCA) were compared by the two-dimensional electrophoresis (2D-PAGE) to proteins from an adjacent non-neoplastic breast tissue. Analysis of multiple gels for each sample identified nine proteins present in the tumor sample that were less present in the matched normal adjacent breast tissue and four proteins present at higher levels in the normal tissue. The altered proteins were identified by matrix assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometry and search in protein databases. Protein disulfide isomerase, BiP protein, calreticulin, cathepsin D, inorganic pyrophosphatase, vimentin, apolipoprotein A1 precursor, tropomyosin 4 and beta5-tubulin were identified as being significantly over-expressed in the IDCA with regard to the normal tissue. The expression of fibrinogen E-fragment (known as anti-angiogenic factor) as well as of fibrin E, Pro2619 and actinG1 was found to be inhibited in the tumor sample. The identified proteins might play an important role during malignant transformation, breast cancer progression, and angiogenesis as well as in cellular signaling. This study demonstrates quantitative and qualitative changes in protein abundance between IDCA and normal tissue. The identification of these differentially expressed proteins could lead to a better understanding of the molecular events linked to breast cancer progression.