BACKGROUND AND OBJECTIVES Histologic margin positivity represents a significant source of adverse clinical outcome affecting breast conservation therapy for in situ or invasive malignancy. Elucidation of factors associated with positive margin status might clarify and improve local therapy strategies. In order to define our experience with margin positivity and to identify relevant pathologic criteria, we retrospectively analyzed the cases of 143 patients who underwent resections for carcinoma with intent of breast conservation between 1995 and 1999. METHODS Histologic features and indices of biologic aggressiveness were compared among tumors resected with positive versus negative margins in order to determine whether such markers could be used to anticipate outcome. RESULTS Twenty-eight pathologic specimens were identified to possess histologically positive margins. Twenty-six patients underwent additional operative procedures. Of the 26 re-excision specimens, 17 (65%) contained residual malignancy. Statistical analysis demonstrated that margin positivity correlated with in situ histology and with Her 2/neu positivity. CONCLUSIONS These data suggest certain pathologic factors that may portend difficulty in achieving negative resection margins in patients in whom breast conservation therapy is considered.