Disseminated malignancies are responsible for the majority of cancer-related deaths. During the metastatic process, circulating tumour cells (CTCs) are generated. The presence of CTCs, epithelial cells found in the peripheral blood, is an essential step in establishing distant metastases. Circulating epithelial cells have the morphology of malignant cells and their number in the blood correlates with tumour burden. To identify CTCs in peripheral blood, two major approaches are used involving additional antibodies and nucleic acid-based techniques. Tumour cells with HER-2 overexpression are frequently resistant to cytotoxic drugs and radiotherapy. Wider clinical application of the detection of minimal residual disease is partly limited by the lack of standardized methods for detection. Recent studies suggest that in addition to the prognostic significance of tumour cells, determination of CTCs may be important in therapy monitoring or as potential targets for targeted therapy. Persistence of minimal residual disease after primary treatment may be an indication for extensive adjuvant treatment in order to prevent relapse of the disease. Detection of CTCs and the use of prognostic markers such as HER-2 overexpression may help us to better understand the biology and clinical significance of the presence of CTCs in breast cancer patients.