Background: Cancer studies were focused mainly on tumor cells. But not that much time passed since researchers began to focus not only on neoplastic cells, but also on significant alterations in the surrounding stroma or tumor microenvironment. These alterations are now recognized as a critical element for breast cancer development and progression, as well as potential therapeutic targets. Different elements of the breast cancer microenvironment (such as immune cells, soluble factors and modified extracellular matrix) act together to stop effective antitumor immunity and stimulate breast cancer progression and metastasis. Stromal cells in the breast cancer microenvironment are characterized by molecular alterations and aberrant signaling pathways, some of which are prognostic factors for clinical outcome. Conclusions: Tissue microenvironment has profound effects on the progression of cancer cells by its paracrine signaling. Molecular characterization of various cell types from the normal breast tissue, ductal carcinoma in situ and invasive breast tumor revealed significant changes in gene profile in all cell types during breast tumor progression. Microenvironment changes influence tumor progression as well as the efficacy of various cancer therapies. There is compelling evidence that the elements of tumor microenvironment respond to different stimuli and release distinct mediators, some antitumorigenic, while others protumorigenic activity. Each of the known players of breast stroma involved in tumorigenesis and cancer progression can be influenced and directed towards an “anticancer” state.