Although micrometastatic tumor cell spread largely determines the prognosis of patients with operable breast cancer, it is usually missed by conventional tumor staging. Several groups (including ours) have therefore developed immunocytochemical and molecular assays that allow the specific detection and characterization of individual carcinoma cells disseminated to bone marrow, blood, and lymph nodes. These assays may improve the prognostic precision of the current classification systems and may provide a tool for the early assessment of the therapeutic effects of anticancer drugs on micrometastatic cells in individual patients. Another aspect of such methods is that they enable detection of tumor cell contamination in stem cell grafts and validation of the efficiency of purging techniques. The most extensive experience exists with immunocytochemical methods, some of which have the potential to serve as a benchmark for less validated molecular methods. Still, the specificity and sensitivity of immunocytochemical detection of single cancer cells are affected by several variables, which include the intricacies of antigen expression, the lack of distinct morphological characteristics, the size of the analyzed sample, and the staining techniques for visualization of antibody binding. This article provides a critical review of the opportunities and pitfalls related to new methods for the detection and monitoring of minimal residual disease in breast cancer.