Maspin is a recently described member of the serpin family of protease inhibitors that is consistently expressed at high levels in mammary myoepithelial cells. This feature was used in the immunohistochemical evaluation of tubular carcinoma (TC) and radial sclerosing lesion (RSL) of the breast, and compared with other markers of myoepithelial cells. Ten cases of TC and 11 cases of RSL were studied for the expression of maspin, alpha-smooth muscle actin (alpha-SMA), metallothionein (MT), and S-100 protein by immunohistochemistry. Myoepithelial cells stained strongly and diffusely for maspin creating a pattern of an outer continuous ring surrounding the epithelium of tubules of all RSLs. This pattern was absent in all TCs; however, the single-layered epithelium comprising the tubules of two TCs was positive for maspin with a moderate to strong intensity. Myoepithelial cells were not positive for MT in a consistent manner. Benign nonproliferative epithelium stained focally and weakly for maspin in four of 11 cases of RSL and was negative for MT in all 11 cases. Foci of mild to moderate epithelial hyperplasia noted in five of 11 cases of RSL stained diffusely with a weak to moderate intensity for maspin and focally with a strong intensity for MT. alpha-SMA was consistently expressed in myoepithelial cells but also in stromal myofibroblasts and blood vessels, creating a pattern that was less satisfactory than maspin in distinguishing RSL from TC. Immunohistochemical staining for S-100 protein was of no differential diagnostic value. In conclusion, immunohistochemical staining for maspin is diagnostically useful and superior to MT, S-100, and alpha-SMA, in distinguishing RSL from TC. The epithelial immunoreactivity for maspin in two of 10 TCs merits further investigation from a prognostic viewpoint.