The diagnosis of metaplastic (sarcomatoid) carcinoma (MSC) of breast often requires immunohistochemistry with a cytokeratin (CK) panel to distinguish them from phyllodes tumors (PT), primary sarcomas, and fibromatoses. CK staining may be heterogeneous in metaplastic carcinomas. The aim of the study was to investigate the theory that MSCs show evidence of myoepithelial differentiation and to evaluate immunohistochemical markers that may be helpful in distinguishing MSCs from PT and fibromatosis. We reviewed histology and performed immunohistochemistry for AE1/AE3, 34betaE12, CK5 and CK14, Cam5.2, CK7 and CK19, epithelial membrane antigen (EMA) (B55), smooth muscle actin (SMA), S100, desmin, vimentin, CD31, CD34, and bcl-2 on paraffin-embedded tissue from 18 MSCs, 26 PTs, and 8 fibromatoses. We assessed staining by using a semiquantitative method. Sarcomatous areas in MSCs were positive for 34betaE12 in 11 cases; for SMA in 10; for CK5 in 7; for CK14 in 6; for Cam5.2, AE1/AE3, and S100 in 5; and for CK7 and CK19 in 3. No CK expression was seen in stromal areas in PT or in fibromatoses. CD34 and bcl-2 were more frequently expressed in spindle cell areas in PTs (18 and 12 of 26, respectively) than in MSCs (0 and 2 of 18, respectively). MSCs show strong evidence of myoepithelial differentiation. CD34 and, to a lesser extent, bcl-2 positivity in PTs may be helpful in differentiating these two lesions from MSCs, particularly in small biopsies, because CK staining in MSCs may be heterogeneous. In our hands, 34betaE12 was the CK most frequently expressed in sarcomatoid areas in MSCs.