The biomarker concordance between core needle biopsy (CNB) and surgical specimen (SS), in breast cancer, has long been a matter of discussion because of its influence on oncologic treatment choice. Particularly, human epidermal growth factor receptor 2 (Her2) status is quite important, because of the impact on breast cancer classification and target therapy. Many factors could influence the difference in biomarker status between samples, such as the technic itself, sample procedures and intratumoral heterogeneity. Neoadjuvant chemotherapy (NAC) can also contribute to this variation and should be taken into consideration. We report a clinical case of a 33-year-old man who was diagnosed with right breast cancer, initially Her2 negative in the CNB. Therefore, the NAC was completed without anti-Her2 treatment. Later, after the mastectomy, revision of the SS was found to be positive for Her2, after the silver in situ hybridization (SISH) technique. Consequently, the patient lost the chance of doing anti-Her2 therapy in the neoadjuvant setting, reducing his possibility to achieve a complete pathologic response and later jeopardizing his clinical outcome.