This report presents our experience with 54 cases of patients who had excision of breast lesions after deployment of radiographic biopsy site markers at the time of stereotactic biopsy. These were of two types: pellets of a resorbable copolymer of polylactic acid/polyglycolic acid (31 cases) and plugs of bovine collagen (23 cases), both containing embedded metallic clips for long-term radiographic marking. On gross examination, the pellets have a characteristic appearance similar to a soft grain of rice, whereas the collagen plugs are spongiform with variable hemorrhagic changes. Microscopically, there are distinct differences in the morphologic features of these two types of biopsy site markers and the associated tissue reactions. With the pellets, there is an initial cell-poor fibrotic reaction around empty spaces followed by a multinucleate giant cell reaction and penetration of the marker core by eosinophilic fibrinous material. The collagen plugs are recognized as eosinophilic, hyalinized, acellular material, accompanied by an inflammatory infiltrate composed predominantly of lymphocytes, plasma cells, eosinophils and, occasionally, neutrophils, which penetrate the core of the marker with time. The degradation of the collagen plug appears to be associated with infiltration of the marker by fibrovascular tissue and deposition of native collagen; of note is the absence of a significant multinucleate giant cell reaction. These novel breast biopsy site markers do not interfere with the histologic processing of the tissue or with their histopathologic interpretation.