The expression of S100 protein, as assessed by immunohistochemistry, has been evaluated in 101 mammary carcinomas of various histological types, including Paget's disease of the nipple. S100 immunoreactivity was seen in 44 of 101 primary carcinomas, including in situ lesions. It was present in all histological types, with the exception of mucoid carcinoma. In the 33 cases with associated Paget's disease of the nipple, S100 expression was seen in the Paget's cells in six cases. S100 immunoreactivity has been suggested as a marker of myoepithelial cells, but in our hands staining of these cells is less consistent using the S100 antibody than with antibodies to actin. Furthermore, S100 protein is also expressed by some luminal epithelial cells. Therefore, in contrast to actin immunoreactivity, S100 immunoreactivity is not a reliable means of differentiating between luminal epithelial and myoepithelial cells. The possibility that staining with antibody to S100 protein may be affected by methods of fixation and immunohistochemical technique is discussed.