Neoadjuvant chemotherapy is becoming the standard of care in locally advanced breast cancers. With complete pathologic response, patients may have a better overall survival. However, most patients do not have a complete pathologic response, and it is unclear how this impacts survival and whether histologic subtype or chemotherapeutic histologic changes play a role. We retrospectively identified 49 cases of invasive breast carcinoma treated with neoadjuvant chemotherapy (40 ductal, nine lobular) and examined histologic and biologic features of ductal and lobular carcinoma before and after chemotherapy. Patients with lobular carcinomas presented at a later age and had lower grade tumors that were more likely estrogen and progesterone receptor positive. Ductal carcinomas had a greater frequency of HER-2/neu amplification and increased Ki-67 rate. After chemotherapy, none of the lobular carcinomas had complete pathologic response compared with 28% of the ductal carcinomas (p = 0.01). Lobular carcinomas had more lymph node metastases. At the time of clinical follow-up, no lobular carcinomas had evidence of disease. Only one lobular carcinoma case had any histologic changes after chemotherapy compared with 37-68% of ductal carcinomas (p < 0.05). In ductal carcinomas, higher grade and negative estrogen receptor expression before chemotherapy and presence of foam cell clusters, HER-2/neu expression, and absence of lymphatic or vascular space invasion after chemotherapy correlated with pathologic response (p < 0.05). Decreased Ki-67 rate after chemotherapy correlated with survival (p = 0.024). Breast biomarker status changed in 9% of all lobular carcinomas and 19% of all ductal carcinomas. Lobular carcinomas respond poorly to neoadjuvant chemotherapy as evidence by lack of complete pathologic response and rare histologic tissue response.