Background: Breast cancer is the most common neoplasm among women in the majority of the developed countries, accounting for one-third of newly diagnosed malignancies. Given the efficiency of neo-adjuvant chemotherapy (NACT) in reducing tumor size, it is logical to assume the same response in axilla. Objective: Our propose was to assess axillary lymph nodes (ALNs) response to NACT using clinical, ultrasound (US) or pathological examinations of sentinel lymph node biopsy (SLNB) or ALN dissection (ALND). Patients and methods: This prospective study included 100 female patients with locally advanced breast cancer (LABC) with clinically palpable or US detectable ALNs. True cut biopsy of primary tumor and fine needle aspiration cytology (FNAC) of ALNs were performed before NACT. Clinical and US response of ALNs was assessed. Surgical local control started with SLNB then ALND in all patients followed by appropriate mastectomy procedure. Primary tumor, SLNB and ALND specimens were submitted for pathological examination. Negative SLN by hematoxylin and eosin (H&E) were subjected to immunohistochemical (IHC) section. Results: Clinical, US and pathological complete response (pCR) to NACT were encountered in 47.1%, 33.3% and 31.4% of patients, respectively. The sensitivity of clinical, radiological, SLNB in predicting pCR were 60%, 82.9%, and 94.1% respectively. US was better than clinical examination in response assessment with accuracy of 78.5% versus (vs.) 60.8%, respectively (p < 0.001). SLNB was more sensitive than clinical examination in predicting pCR with accuracy of 94.9%. The detection rate of SLN was 76.5%. Conclusions: pCR post NACT is high enough to make axillary conservation worthwhile. US and SLNB can assess and predict nodal response with accepted accuracy rate and SLNB is feasible after NACT.