The identification of an outer layer of myoepithelial cells is a valuable clue in the differential diagnosis of breast lesions. Myoepithelial cells can usually be appreciated with standard hematoxylin-eosin stains, however in pathology practice one encounters difficult cases, particularly in core biopsy specimens. There are several reported markers for the immunohistochemical detection of myoepithelial cells. Smooth muscle specific proteins, such as smooth muscle actin, smooth muscle myosin heavy chain, calponin and h-caldesmone are utilized to highlight myoepithelium. Smooth muscle actin is the most commonly used and has been established as a specific and sensitive marker. However, sometimes the staining can not be interpreted, since actin stains stromal fibroblasts and vascular smooth muscle cells as well. S100 protein and specific cytokeratins (keratins 5,7,14 and 17) also stain myoepithelial cells, but the staining is not specific and is not optimally sensitive. Maspin and CD10 are relatively new and promising markers. The nuclear protein p63 has attracted much attention in recent reports. p63-positive myoepithelial cells have been shown to surround benign epithelial lesions and form a consistent, although discontinuous, rim around epithelial cells in carcinomas in situ. No staining has been noted in infiltrative carcinomas. p63-immunostaining is nuclear and so it is easily appreciated, even in cytologic preparations. It is also highly specific since neither stromal fibroblasts nor vascular smooth muscle cells are stained. In conclusion, it appears that p63 is a sensitive and specific myoepithelial marker and may be included in immunohistochemical panels aiming at identifying myoepithelial cells in problematic breast lesions.