Treatment strategies in oncology are nowadays largely based on the "target therapy model", which allows to personalize the cure of each patient depending on distinctive host and disease features. As a general concept "targeted drugs" are effective only when the tumor exhibits the "target", which in breast cancer pathology may correspond to the expression of estrogen receptors and/or of HER2. These biomarkers are evaluated on breast cancer tissues by companion diagnostic tests, however, evidence suggests that the first step in breast cancer predictive pathology is still represented by morphology. For instance, histological types, such as tubular and cribriform carcinomas, define patients who may not need any treatments other than surgical excision. Neoadjuvant studies have shown that patients affected by lobular carcinomas are not likely to have any beneficial effects from chemotherapy. The second step in prediction is represented by immunophenotyping. If the immunohistochemical evaluation of four markers (estrogen and progesterone receptors, HER2 and Ki67) remains the best practice for breast cancer predictive pathology, molecular pathology has certainly reshaped the way we approach breast cancer diagnosis. The aim of this review is to discuss current knowledge in predictive pathology for the management of breast cancer patients, focusing on the benefits and drawbacks of traditional tools and of novel improvements of molecular biology.