To evaluate the osteopontin (OPN) protein expression levels in breast carcinomas to determine if they correlate with mammographic appearances such as calcifications. This retrospective study was institutional review board approved. Informed consent was obtained from patients. Clinical history, histopathologic findings, mammographic features, and OPN expression as determined with immunohistochemistry results were evaluated in 141 women with breast cancer. The median age of patients was 53 years (range, 29-82 years). Mammographic features and clinicopathologic characteristics were correlated with tumor OPN expression. chi(2) And Fisher exact tests were used to evaluate the association of OPN expression with mammographic and clinicopathologic features. Calcifications on mammograms (P = .012), spiculated margins of mass on mammograms (P = .02), "triple-negative" (ie, cancer that is estrogen receptor, progesterone receptor, and human epidermal growth factor receptor negative) phenotype (P = .02), and lymph node metastasis (P < .0001) were significantly associated with OPN status. In contrast to OPN-negative tumors, OPN-positive tumors were more likely to have spiculated margins (57.6% vs 9.2%), to be associated with calcifications (54.3% vs 30.6%), to be a triple-negative phenotype (26% vs 8.1%), and to have axillary lymph node metastasis (81.5% vs 38.8%). Most calcifications were of pleomorphic morphology (60.4% vs 11.8%, P = .046). OPN could play a role in the formation of calcifications that often are associated with breast cancer.