PURPOSE: The goal of the current study is to help refine guidelines for the need for re-excision and the appropriate amount of breast tissue to re-excise in patients with early breast cancer following excisional breast biopsy when treated with breast-conserving therapy (BCT). PATIENTS AND METHODS: The study population consisted of 441 patients derived from a dataset of 607 consecutive cases of stage I and II breast cancer treated with BCT, in which patients underwent primary excisional diagnostic biopsy and subsequent re-excision prior to the initiation of radiation therapy (RT). A single pathologist reviewed all specimens. Re-excision was indicated because tumor was found close to or involving the resection margin. In 333 of the 441 cases, it was possible to measure the extension of carcinoma into the re-excision specimen. Margins were classified as negative (carcinoma>4.2 mm from the margin), near (<4.2 mm from the margin) or positive. Any carcinoma identified near the final margin was quantified by width of invasive carcinoma and number of ductal carcinoma in situ (DCIS) ducts near the margin and subdivided into three distinct groups: least, intermediate, and greatest amount. These factors were then analyzed to determine the likelihood and extent of residual carcinoma in re-excision specimens. Statistical analysis was performed using Systat version 10 (SPSS Inc., Chicago, IL). RESULTS: The quantity of carcinoma near the initial biopsy margin and the invasive carcinoma-to-specimen dimension ratio demonstrated a significant association with increasing amounts of residual carcinoma at re-excision. Combination of these two variables allowed for a statistically significant (P<0.001) calculation of risk index for identifying significant residual invasive carcinoma or DCIS in the adjacent breast parenchyma at re-excision, and yielded stratification into low- (6%), intermediate- (27%), and high-risk (44%) groups. In re-excision specimens, the observed distance of carcinoma extension into adjacent breast tissue was associated with a statistically significant decrease in the ratio of the initial excisional biopsy specimen dimensions and invasive carcinoma dimensions. Combining the initial margin status with the specimen-to-invasive carcinoma maximum dimension ratio yielded an accurate predictor of the maximum distance of tumor extension. CONCLUSIONS: Evaluation of the initial excisional biopsy margin status in correlation with the invasive carcinoma-to-specimen maximum dimension ratio may be helpful for (1) identifying patients who require re-excision prior to RT and (2) predicting the quantity of additional breast tissue to excise to ensure adequate surgical margins with BCT.