Columnar cell lesions of the breast are increasingly recognized at mammography for their tendency to calcify. We studied 392 vacuum-assisted core biopsies performed solely for calcifications to evaluate the frequency of columnar cell lesions, their relationship with radiological risk, appearance of calcifications, and clinical data. Management and follow-up of columnar cell lesions without and with atypia (flat epithelial atypia) was analyzed. Cases with architectural atypia (cribriform spaces and/or micropapillae) were excluded from flat epithelial atypia. Calcifications were within the lumen of acini affected by columnar cell lesions in 137 out of 156 biopsies diagnosed with some columnar cell lesions. These represented 37% of vacuum-assisted core biopsies and 62% of low radiological risk (BI-RADS3) calcifications. High-risk (BI-RADS5) calcifications were never associated with columnar cell lesions. Age and menopausal status were comparable in columnar and in not-columnar cell lesions. Atypia was associated with long-term hormone replacement therapy in both lesions. Surgical biopsy was recommended for all cases with atypia. Flat epithelial atypia, as the only histological findings on vacuum-assisted core biopsies, was never associated with malignancy at surgery. In conclusion, we suggest that surgical excision is not mandatory when flat epithelial atypia is found as the most advanced lesion on vacuum-assisted core biopsy performed for low radiological risk calcifications, and that women should be advised of the possible hormone dependency of this entity. Modern Pathology ( Keywords: columnar cell lesions; flat epithelial lesion; calcifications Stereotactic vacuum-assisted core biopsy is currently used to diagnose indeterminate or suspicious breast calcifications that are histologically related to a spectrum of breast lesions encompassing ductal carcinomas in situ and preneoplastic and benign lesions. Often this type of calcification resides in so-called 'columnar cell lesions', 1 entities characterized by the presence of columnar epithelial cells lining the terminal duct lobular units that typically show flocculant or secretory material and microcalcifications in the lumen. The Breast Imaging Reporting and Data System (BI-RADS) 2 has standardized the description and management of findings identified on mammograms, thereby facilitating communication between radiologists and referring physicians. However, to our knowledge, there are no specific studies evaluating whether specific calcification descriptors are associate with columnar cell lesions.Columnar cell lesions have been described under a variety of names. [3][4][5][6][7] According to Schnitt and Vincent-Salomon, 1 columnar cell lesions have been grouped into the categories of columnar cell change and columnar cell hyperplasia without or with atypia. Other authors 8 have proposed a subcategorization of columnar cell lesions depending on the presence of architectural and/or cytological atypia. The unifying term 'flat epithelial atypia' has been proposed by ...