The knowledge of specific genetic changes and their biological consequences is critical to an understanding of the natural history of breast tumors and the development of rational means to prevent and treat them. A number of genetic changes have been identified in breast tumors. Some of these involve specific genetic loci that directly contribute to one or more attributes of transformation, i.e., dysregulated proliferation and invasion, while other changes confer genetic instability that increases the possibility of acquiring subsequent, specific genetic lesions relevant to tumorigenesis. Many of these changes have been correlated with an adverse prognosis and attempts to integrate these in comprehensive multifactorial prognostic models are in progress. Initial clinical trials have also demonstrated the 'proof of concept' of targeting specific genetic lesions for therapeutic purposes. In the not too distant future, we can envision the use of specific therapies for individual (or subgroups of) tumors based on the specific genetic changes that lead to their development, rather than the global approach of multiagent cytotoxic therapy that is in widespread use today.