Survivin, a novel inhibitor of apoptosis, is expressed in a variety of human cancers, with reports of prognostic significance in some neoplasms. The authors' aim was to evaluate survivin expression in a spectrum of breast lesions to determine differential expression in malignant versus benign lesions and its potential role as a diagnostic or prognostic marker. The authors found that survivin is expressed in breast tissue in the full spectrum of normal to invasive carcinoma. It is predominantly nuclear with a faint cytoplasmic blush. Survivin expression was independent of patient age and tumor size. Benign breast tissue showed survivin expression in a lower percentage of cells (45%) than malignant lesions. The median values for the percentage of cells that stained for survivin were statistically different among the categories of invasive carcinoma, DCIS, LCIS, and benign breast tissue (P < or = 0.001). The highest percentage of positive-staining cells was seen in high-grade DCIS (95%). The authors found a trend toward a higher percentage of cells staining for survivin in breast carcinoma cases that were ER negative, PR negative, or Her2/neu positive, although this was not statistically significant. Survivin expression was preserved in biopsies from recurrent tumors without loss of nuclear survivin expression. In conclusion, survivin is overexpressed in malignant breast lesions relative to benign lesions or normal breast tissue and in high-grade DCIS relative to nonhigh-grade DCIS. Therefore, survivin may have a role, albeit a limited one, as a prognostic marker in breast lesions.