PURPOSE: Clinically palpable lymph nodes (CPLN) are usually considered a contraindication to sentinel lymph node biopsy (SLNB) but one third of these patients are node negative. The aim of the present study is to evaluate the clinical usefulness of combining SLNB and preoperative axillary ultrasonography (AUS) with FNAC in patients with clinically palpable but indeterminate axillary lymph nodes. MATERIALS AND METHODS: Fifty three patients with primary breast cancer and CPLN (mean age, 51.6 years; median age 51 years; age range, 28-73 years) were included in the study. All patients underwent AUS and fine needle aspiration (FNAC) followed by SLNB in FNAC negative patients (Group A). Patients with proven metastasis subsequently had axillary lymph node dissection (ALND) (Group B). Standard SLN scintigraphy was performed 2-4h before surgery by injecting Tc-99m labeled nano-colloid intra-dermally in the periareolar region. RESULTS: Nodal metastases were documented at FNAC in 26 (49%) of the 53 patients with subsequent ALND (Group B). All 27 patients (51%) with negative FNAC results (Group A) underwent SLNB, which revealed metastasis in 6 (11%) patients. The remaining 21 (40%) patients were tumor negative and all these patients remain disease free during the follow-up period of 12-36 months with NPV of 100%. SLN was identified in all patients (100% success rate). Preoperative AUS sensitivity was 78%, specificity 76%, PPV 83%, NPV 69% and accuracy 77% (p=0.001). In comparison, ultrasound guided FNAC sensitivity, specificity, positive predictive value, negative predictive value and accuracy were 81%, 100%, 100%, 78%, 89% respectively (p=0.001). CONCLUSIONS: The inaccuracy of clinical assessment allows widening of indication of SLNB. Preoperative ultrasonography and guided FNAC can help in selecting the patients suitable for ALND or SLNB. Patients who are FNAC positive can proceed to ALND whilst FNAC negative samples can undergo SLNB. This combination strategy may be helpful in avoiding unnecessary ALND.