Mammary carcinoma diagnosed by large-core stereotactic biopsy (LCSBB) is often followed by definitive surgery. We report on positive (malignant) LCSBB followed by definitive surgery that failed to demonstrate malignancy. Between January 1993 and August 1996, 206 women in our institution underwent LCSBB. Carcinoma was diagnosed in 45 patients (22%) of the 206 (ductal carcinoma in situ (DCIS), n = 12; invasive carcinoma, n = 33). Twenty-nine of the 45 patients subsequently underwent mastectomy, and 8 of 45 underwent lumpectomy. In 34 (92%) of these 37 patients, carcinoma was demonstrated at follow-up surgery, but in 3 patients (8%), mastectomy failed to reveal carcinoma. The characteristics of these three patients are as follows: Patient 1 was a 58-year-old woman with a nonpalpable 6- to 8-mm nodule revealed by a screening mammogram. Three of 8 LCSBBs showed colloid carcinoma, but histologic examination of 50 paraffin blocks and radiographic examination of the mastectomy sample failed to reveal carcinoma. Patient 2 was a 64-year-old woman with a nonpalpable 6- to 9-mm nodule revealed by mammogram. Six of 12 LCSBBs showed tubular carcinoma, but histologic examination of 30 paraffin blocks from her mastectomy sample failed to reveal carcinoma. Patient 3 was a 72-year-old woman with a history of DCIS. She had undergone a lumpectomy and radiotherapy, and she had suspicious ipsilateral microcalcifications. Two of 8 LCSBBs showed comedo DCIS, but histologic examination of 26 paraffin blocks and radiographic examination of the mastectomy sample failed to reveal carcinoma. Possible explanations for a mastectomy without malignancy after carcinoma was diagnosed by LCSBB include removal of the entire lesion by LCSBB, inflammatory response obliterating remaining tumor, false-positive core biopsy result, patient misidentification, inadequate sampling of the surgical specimen, and failure to remove the tumor. We outline a series of steps for the pathologists to follow when confronted with such a case.