Introduction: Management of nipple discharge (ND) is variable reflecting the lack of a uniformly accepted assessment policy. The aim of this study was to determine the common underlying pathology in patients presenting with ND as well as to evaluate the diagnostic role of red blood cells (RBC) and epithelial cells in the nipple cytology (NC). Methodology: Electronic data base held at Leeds Teaching Hospitals NHS Trust was searched to identify all the patients who underwent Hadfield’s (open diagnostic major duct excision) procedure for ND from January 2004 to December 2009. We included only patients with ND as the primary symptom and excluded those with any underlying palpable or radiological abnormality. Results: Hadfield’s procedure was performed in 120 cases (Median age=49 years; range=20-88). The final histology showed benign changes (duct ectasia/hyperplasia and fibrocystic changes) in most (37.5%), followed by intra-ductal papilloma (32.5%), normal (16.6%), malignant (10.9%) and atypical (2.5%) changes in the rest. The presence of RBC in NC was 87% sensitive to detect any underlying pathology and 69% sensitive to predict malignancy at the expense of specificity. However, epithelial cells were found to be neither sensitive nor specific enough to detect underlying pathology or malignancy. Conclusion: The aetiology remains benign in most patients presenting with ND in the absence of any underlying palpable or radiological abnormality. Even in patients without an underlying radiological abnormality, diagnostic surgery should be offered if RBC is present in the nipple cytology.