Neuroendocrine breast carcinomas are rare but may represent either metastatic or primary lesions. So far, clinical and preoperative histopathological examinations do not distinguish properly between a primary or metastatic breast tumor. Due to any possible consequences following an appropriate treatment, markers which may be helpful for such a distinguishment are needed. We addressed this study in order to evaluate the immunohistochemical expression of GCDFP-15 and mammaglobin in a subset of pure neuroendocrine breast carcinomas (n = 9) and compared the expression profile with a cohort of non-mammary neuroendocrine tumors (n = 99). We observed in our study that solid neuroendocrine breast carcinomas are characterized by the expression of estrogen and progesterone receptors as well as GCDFP-15 and/or mammaglobin. GCDFP-15 was expressed in 6 out of 9 cases, mammaglobin was positive in 4 out of 9 tumors. In contrast, neuroendocrine tumors of the non-mammary cohort expressed neither GCDFP-15 nor mammaglobin. We conclude that mammaglobin and GCDFP-15 as markers of epithelial breast origin may work as a new and reliable diagnostic tool to distinguish primary endocrine tumors of the breast from a metastatic neuroendocrine disease. This is of utmost importance, especially for surgical management.