Purpose Acceptance of breast conservation surgery (BCS) is low among Indian women, as many perceive mastectomy to be a superior cost-effective surgical option. Obtaining uninfiltrated margins is vital during BCS. The need for reoperation to re-excise infiltrated surgical margins adds to the cost of treatment, which further reduces the acceptability of BCS. Intraoperative frozen-section (FS) histology assessment of margins provides an opportunity to carry out a single-stage, safe BCS; however, the utility of FS margin assessment remains unproven because of its perceived low accuracy, added costs, and longer operating time. In this retrospective analysis, we studied the accuracy of FS for margin assessment, its ability to help avoid reoperations, and the cost effectiveness of one-step BCS using FS compared with margin assessment using postoperative paraffin section (PS) histopathology. Methods Patients who underwent BCS during 2011 to 2015 with a minimum 1-year follow-up were included. All patients underwent intraoperative FS and postoperative PS margin assessment. All infiltrated margins were re-excised. Repeatedly infiltrated re-excised margins or extensive ductal carcinoma in situ necessitated mastectomy in few patients. We evaluated the accuracy of FS in the detection of margin infiltration, thereby allowing single-stage, safe BCS. The cost effectiveness of two strategies for the management of infiltrated margins, namely intraoperative FS and single-stage margin excision/mastectomy and postoperative PS and reoperation (two-step) surgery, were compared. The cost per saved reoperation with the use of intraoperative FS was calculated using actual hospital costs and various—lower and higher—cost assumptions. Results On the basis of intraoperative FS margin assessment, 18 (12.5%) of 144 patients required margin(s) re-excision and another nine patients (6.2%) needed mastectomy. Twenty-six patients (18%) were thus spared reoperation with the use of FS. Two patients (1.4%) with uninfiltrated margins on FS—false-negative FS—needed reoperation for infiltrated margins that were detected on PS. Considering the costs (144 FS and two reoperations) and savings (26 avoided reoperations), use of FS was 1.15 times more cost effective than PS for achieving uninfiltrated margins. Cost incurred per saved reoperation by FS was INR 5,438 (approximately $81 USD). Sensitivity analysis using various cost assumptions revealed similar results. Conclusion Use of FS can facilitate single-step, oncologically safe BCS by avoiding reoperation in those patients with infiltrated margins and is cost effective compared with postoperative margin assessment using PS alone. FS can thus help in improving the acceptability of BCS, even in those patients with relatively large tumors for whom the possible need and cost of reoperation are major deterrents against BCS. AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/jco/site/ifc . No COIs from the authors.