Cystic hypersecretory carcinoma (CHC) is an uncommon variant of ductal carcinoma in situ characterized by, among other features, the presence of luminal secretion resembling thyroidal colloid. CHC is thought to behave in an indolent manner but has the potential to give rise to invasive carcinoma, which is often poorly differentiated. We studied the immunohistochemical, clinical, and morphologic features of 10 cases of CHC. All patients were women averaging 62.8 years in age (range, 47 to 79 y). The clinical/radiographic presentation was a mass (5/10), calcifications (3/10), bloody nipple discharge (1/10), and unknown (1/10). Microscopic size of CHC ranged from 0.2 to 2.7 cm (mean, 0.9 cm). Micropapillary growth was present in all cases. Nuclear grade was intermediate (5/10) or high (5/10). One case also showed microinvasive carcinoma. All cases arose in a background of cystic hypersecretory hyperplasia (CHH) and/or CHH with atypia. CHC was ER in 8/10 cases (ER+/PR+, 4/10; ER+/PR+, 4/10). Two cases were ER-/PR-, including the case with microinvasive carcinoma. All were HER2-. Androgen receptor was expressed in 3/10 (30%) cases. Myoepithelial stains p63, smooth muscle myosin, and CK5 showed circumferential staining in 9/10 (90%) cases, whereas 1 case was negative for p63, smooth muscle myosin, and CK5 in both CHC and adjacent CHH. Basal-like carcinoma markers EGFR, CK14, and CK5 were negative in all cases, with the exception of 1 case that was positive for EGFR. Four patients with follow-up information showed no evidence of disease (mean, 5.5 y). CHC is a distinct variant of ductal carcinoma in situ that arises in a background of CHH and is characterized by micropapillary growth, intermediate-grade to high-grade nuclei, and luminal colloid-like secretion. CHC is usually ER and HER2-. Negative or discontinuous reactivity with myoepithelial markers may be seen, despite its in situ nature. CHC usually behaves in a nonaggressive manner as was seen in our patients who were all free from disease at last follow-up.