There is currently great interest in the detection and characterization of putative precursor breast cancer lesions because of the possibility of chemoprevention. Knowledge of the biologic features of premalignant lesions, although limited, is rapidly evolving. Premalignant breast lesions have been examined for the presence of genetic alterations and for the expression of biomarkers such as the estrogen receptor (ER), Ki67, p53, and HER2/neu. Data obtained from genetic studies of precursor breast lesions clearly support the contention that genetic alterations begin quite early in selected subsets of histologically benign lesions. Although the results of biomarker expression profiles have been contradictory, most studies agree that precursor lesions significantly overexpress ER and that progressive alterations in ER expression accompany the transition of normal cells to hyperplastic lesions and carcinoma in situ. So far, the collected evidence indicates that precursor lesions in the breast demonstrate biomarker expression profiles and genetic abnormalities that are distinct from those of terminal ductal lobular units but share some of these features with invasive tumors. Future research in this field is urgently needed to identify specific biomarkers of prognostic and predictive value, which can help not only in the selection of patients for chemopreventive therapy but in monitoring the progression of high-risk lesions.