ER-positive, HER-2-negative operable breast cancer represents a heterogeneous group of tumors. Tumor subtypes associated with different responses to neoadjuvant therapies can be identified through the evaluation of pathological features that include grade, the degree of expression of estrogen (ER) and progesterone (PgR) receptors and markers of cell proliferation such as Ki67 labeling index. For patients with a high proliferative index and/or a high grade who have a higher likelihood for a pathologic complete response, the selection of neoadjuvant chemotherapy should follow the same algorithm utilized for postoperative adjuvant treatments. In particular, both anthracyclines and taxanes should be evaluated for the chemotherapy regimen. Neoadjuvant endocrine therapy should be considered in place of cytotoxic neoadjuvant therapy for postmenopausal patients with tumors with low grade or proliferation and high ER and PgR expression. If given, such treatment should be continued for a minimum of 4-8 months. Selected patients with special types of breast cancer (e.g. pure tubular, cribriform and mucinous tumors) have a limited expected benefit from preoperative therapy and might receive adjuvant endocrine therapy alone. Tailored neoadjuvant treatments should be considered in patients with ER-positive tumors. Issues focusing on safety, quality of life and patient preference should be routinely discussed.