We have noted in breast biopsies performed for microcalcifications a spectrum of lesions in the terminal duct lobular unit (TDLU) characterized by columnar epithelial cells with prominent apical cytoplasmic snouts, intraluminal secretions, and varying degrees of nuclear atypia and architectural complexity. The appearance of some of these lesions is worrisome, but diagnostic difficulties arise because the histologic features do not fulfill established criteria for the diagnosis of atypical ductal hyperplasia or ductal carcinoma in situ (DCIS). We have termed such lesions columnar alteration with prominent apical snouts and secretions (CAPSS). The purpose of this study was to define the pathologic spectrum and mammographic features of these lesions. We reviewed histologic sections and mammograms from 100 consecutive breast biopsies performed for microcalcifications. The prevalence and histologic features of CAPSS and the association with other histologic findings were recorded. CAPSS was identified in 42% of cases. At the lower end of the spectrum were lesions similar to columnar alteration of lobules but in which apical cytoplasmic secretion and nuclear stratification were more pronounced and cells with a hobnail configuration were common. More advanced lesions showed columnar epithelial cell tufts, bridges, and micropapillations with prominent apical cytoplasmic snouts and with greater degrees of nuclear stratification and atypia. At the upper end of the spectrum were lesions that could arguably be considered DCIS. Calcifications were present within CAPSS in 74% of cases, were frequently psammomatous, and were typically nonbranching and often round on mammography. Columnar alteration of lobules was more common in biopsies with than without CAPSS (74 versus 36%, p < 0.001). Ductal carcinoma in situ was seen with similar frequency in biopsies with and without CAPSS (38 versus 41%). However, DCIS in cases with CAPSS was more often of the low-grade micropapillary-cribriform type than in cases without CAPSS (56 versus 17%, p < 0.01), and CAPSS and DCIS commonly coexisted in the same or adjacent TDLUs. In conclusion, 1) CAPSS encompasses a spectrum of lesions bounded at the lower end by columnar alteration of lobules and at the upper end by low-grade DCIS. Lesions recently described by Page as "hypersecretory hyperplasia with atypia" fall within this spectrum. 2) Some CAPSS lesions present architectural or cytologic features that create diagnostic difficulties and raise the possibility of atypical ductal hyperplasia or DCIS; however, the level of cancer risk associated with CAPSS lesions that do not fulfill established criteria for atypical ductal hyperplasia or DCIS is unknown and requires evaluation in follow-up studies.