Aim To analyze the histopathological outcome of stereotactic biopsies of newly developed suspicious calcifications at lumpectomy scar site in patients with breast conservation surgery (BCS) to determine the incidence of malignancy and the association of mammographic appearance of recurrent microcalcification and their distribution. We also determined the association of disease recurrence with the presence of calcifications in original tumor and lumpectomy resection margins with the risk of recurrence. Materials and methods This study is a retrospective review of mammograms of patients with breast cancer from 2010 to 2021 who underwent stereotactic biopsy of newly developed suspicious calcifications at scar site appreciated on annual follow-up mammogram after breast conservation surgery (BCS) with no mass on correlative ultrasound. The radiological and pathological features of the patients' primary tumor and new calcifications were obtained from the hospital's electronic patient record system. Results A total of 84 patients with breast cancer developed suspicious microcalcifications at the lumpectomy scar site detected on follow-up mammograms after BCS, and 28.6% showed malignant histopathological outcomes. All malignant cases demonstrated pleomorphic morphology. All amorphous (9.5%) and coarse heterogeneous (54.8%) calcifications were benign. The distribution pattern of recurrent malignant calcifications was grouped in 9.5%, regional in 2.4%, linear in 9.5%, and segmental in 7.1%. Calcifications in primary tumors were found in 20.2% of cases. Positive margins were found in 7.1% of these malignant cases. Statistically, there was a strong association between calcification morphology, calcification distribution, presence of calcifications on baseline mammogram, and tumor resection margins. The presence of calcifications in primary tumors and positive resection margins were identified as significant independent risk factors of malignant recurrent calcifications in the logistic regression model and marginal statistical significance in the multivariable logistic regression (MLR) model. Conclusion The interval development of pleomorphic calcifications after BCS with either linear or segmental pattern, positive resection margins, and associated calcifications in primary tumors was related to the increase in the risk of recurrence. Although amorphous and coarse heterogeneous morphology with grouped distribution showed benign outcomes, stereotactic biopsy is recommended to exclude disease recurrence in this high-risk patient population.