Alpha-lactalbumin (ALA), a milk protein, was demonstrated by immunohistochemistry with polyclonal antisera from three different sources in primary and metastatic breast carcinomas, and mammary Paget's disease. ALA localization was observed in 67% of mammary carcinomas, and in 62% of their metastases to sites which included lymph nodes, lung, bone, liver, pericardium, skin, and subcutaneous tissue. There was close correlation between primary and metastatic breast carcinomas in ALA positivity, but no correlation between ALA positivity and histologic differentiation. A variety of nonmammary neoplasms were examined for ALA immunoreactivity. In contrast to ALA immunoreactivity of breast tissue, which was removed by preabsorption of antiserum with ALA antigen, a number of skin appendage tumors, salivary gland tumors, and mesotheliomas demonstrated positive staining which was not abolished by preabsorption and was most likely due to the presence of cross-reacting antibodies. One commercial ALA antiserum also reacted with pancreatic islet cells in a distribution similar to glucagon. Our results demonstrate the presence of ALA in breast carcinomas and its potential value to the surgical pathologist in the workup of metastatic carcinomas of unknown primary sites. However, the staining encountered in some nonmammary tumors necessitates caution in its interpretation.