Despite modern therapy, one third to one half of patients who get breast cancer will eventually die from it. This disconcerting circumstance has focused attention on prevention, and preventing breast cancer will require a much better understanding of the biological abnormalities underlying its development and progression. Many studies into the mechanisms of invasive breast cancer evolution have evaluated presumed precursor lesions (e.g. proliferative disease without atypia, atypical ductal hyperplasia, and ductal carcinoma in-situ) for genetic alterations known to occur in fully developed invasive carcinomas. This approach has shed some light on events which may be important in early malignant transformation, including the observations that overexpression of the c-erbB-2 oncogene and mutations of the p53 tumor suppressor gene are present in significant subsets of DCIS, but not PDWA or ADH. Although this approach is limited by our incomplete knowledge of cancer genetics, there is still a great deal to learn about breast cancer evolution by evaluating cancer-associated genes in potential precursor lesions using established techniques such as immunohistochemistry and in situ hybridization.