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P40 antibody has been shown to be a more specific squamous and basal cell marker compared with p63. As detection of myoepithelial cells (MECs) plays a critical role in breast pathology, and the fact that p40 targets an isoform of p63, this study was designed to compare these antibodies in a variety of lesions, especially those with an sclerotic stroma and carcinoma in situ. All studied lesions were selected from the daily cases of the 3 authors and stained with p63, p40, and calponin immunohistochemical stains. Thirty-four cases (and 19 internal controls) were included. Seventy percent constituted sclerotic lesions (12 cases) and ductal carcinoma in situ (12 cases). P40 and p63 stained all lesions and showed a similar patchy staining pattern in 50% of ductal carcinoma in situ and sclerotic lesions. Compared with internal controls, p40 and p63 demonstrated decreased staining intensity in up to 70% and 8% of all cases, respectively, with no cross-reactivity with mesenchymal cells and minor cross-reactivity with epithelial cells. In our study, p40 did not outperform p63 as a MEC marker. p40 showed a decreased intensity in a higher number of cases (P<0.0001). In our opinion, p63 continues to be the best nuclear marker for the detection of MECs in the daily practice of breast pathology.