Background: BRCA mutation carriers have an elevated lifetime and interval breast cancer risk. We sought to compare BRCA mutation carriers with screen-detected versus clinically detected, interval breast cancers. Methods: Women with a known BRCA mutation prior to a breast cancer diagnosis were identified. Clinical and pathologic factors, and imaging within 18 months of diagnosis were compared among screen-detected vs clinically detected/interval cancers. Clinically detected tumors were those detected by physical exam regardless of screening history, whereas interval cancers were those detected by physical exam among women undergoing regular screening. Results: Of 115 breast cancers, 93 were screen and 22 clinically detected, of which 11 were interval cancers among regular screeners. Women with clinically detected/interval cancers were younger, had lower BMIs, and were more likely to be Black than those with screen-detected cancers (p < 0.05). Clinically detected/interval cancers were all invasive, were larger, more likely to be node positive and to have lymphovascular invasion, and were more likely to require axillary lymph node dissection and chemotherapy (p < 0.05). No significant differences were seen by BRCA mutation, mammographic density, MRI background parenchymal enhancement, tumor grade, or receptor status between cohorts. Women screened with both mammogram and MRI had significantly lower rates of clinically detected/interval cancer rates compared to women screened with only mammogram or MRI alone (p < 0.05)(Table). Conclusions: Clinically detected/interval breast cancers among BRCA mutation carriers have worse clinicopathologic features than screen-detected tumors, and require more aggressive medical and surgical therapy. Imaging with mammogram and MRI is associated with lower interval cancer development and should be utilized among this high-risk population.