Metastatic spread of breast cancer begins with the dissociation of cancer cells from the primary tumour. The dissociated cancer cells either settle in or trespass through the tissues/organs that they encounter, thus leaving residual or micro-metastasis in the tissues or organs. Detection of the residual cells and micro-metastasis in tissues or organs other than the originating tissues and circulating cancer cells constitutes an important aspect in staging, predicting prognosis and design therapy. However, the size of micro-metastasis and number of tumour cells, particularly in the circulation and bone marrow have presented a challenge for reliably and sensitively detecting them. Recent development in technology, including quantitative DNA sequence detection has increased the prospect for detection in this area. Recent studies have shown that molecular detection of micro-metastasis disease from lymph nodes, bone marrow, and the blood circulation can provide very valuable information for the presence of micro-residual disease and its impact on tumour progression and clinical outcomes. The current article discusses recent developments, in the detection of micro-metastasis using molecular biology techniques.