Objective: This systematic review was conducted to provide treatment recommendations for patients with a diagnosis of columnar cell lesions (CCLs) in a breast core needle biopsy (CNB). Background: CCLs are putative breast cancer precursors and are often associated with (in situ) carcinoma in excision specimens. Although several studies reported on the progression risk and underestimation rate of a CNB diagnosis of CCL, there is no consensus regarding optimal clinical management in this context. Methods: We searched MEDLINE, Embase, and Cochrane databases from 1990 to October 2010 for studies on patients with a CNB diagnosis of CCL without atypia, CCL with atypia and atypical ductal hyperplasia associated with CCL followed by surgical excision or clinical follow up. Results: Of 1759 selected articles, 24 were included in this review. The pooled underestimation risks for (in situ) carcinoma were as follow: CCL without atypia 1.5% (95% confidence interval [CI] 0.6%-4%), CCL with atypia 9% (95% CI: 5%-14%), and atypical ductal hyperplasia associated with CCL 20% (95% CI: 13%-28%), based on the whole groups of patients with a CNB. Studies including CCLs with long-term clinical follow-up showed a trend toward a limited elevated breast cancer risk. Conclusions: On the basis of the (in situ) carcinoma underestimation rates of patients with a CNB diagnosis of CCL with atypia and atypical ductal hyperplasia associated with CCL, surgical excision should be considered. For CCL without atypia, more studies with a long-term follow-up are required, but so far, surgical excision biopsy does not seem to be necessary.