A grossly and microscopically distinctive multicystic form of duct carcinoma of the [human] breast which was termed cystic hypersecretory duct carcinoma is described. The outstanding morphologic feature is marked secretory activity with the formation of dilated ducts and cysts containing homogeneous, eosinophilic material which resembles thyroid colloid. The inconspicuous epithelium lining the cysts gives rise to micropapillary carcinoma which also occurs in associated ducts. A biopsy that consists entirely of cystic elements, lacking the papillary component, should be termed cystic hypersecretory hyperplasia rather than carcinoma. This may be a persistent condition with the potential to evolve into carcinoma. Eight patients with cystic hypersecretory duct carcinoma were studied, ranging in age from 32-78 yr (mean 54). In 2 cases there was coexistent invasive carcinoma, presenting as inflammatory carcinoma with bone metastases in 1 women and with a single axillary lymph node metastasis in another. Six patients with intraductal carcinoma treated with mastectomy or local excision have remained well, the longest follow-up being 2 yr. Histochemical studies were negative for thyroglobulin in all cases studied. Some lesions were positive for 1 or more of the following: mucin by mucicarmine stain; carcinoembryonic antigen; .alpha.-lactalbumin; mouse mammary tumor virus GP52 antigen. Cystic hypersecretory duct carcinoma is morphologically distinguishable from juvenile (secretory) carcinoma and from mucinous (colloid) carcinoma. Longer follow-up and study of additional cases will be necessary to determine if this lesion has distinctive clinical characteristics.