ObjectiveTo compare the effectiveness of sequential method pure single-port lumpectomy-breast conserving surgery (SMPSL-BCS) in treating early-stage breast cancer patients with tumors in different quadrants. Methods A retrospective analysis was conducted on 200 early-stage breast cancer female patients admitted between January 2023 and December 2023. According to the quadrant where the tumor was located, the patients were allocated into the upper outer quadrant group (UO group), lower outer quadrant group (LO group), upper inner quadrant group (UI group), and lower inner quadrant group (LI group), with 50 cases in each group. There was no significant difference (P>0.05) in the baseline data, including age, body mass index, smoking history, marital status, comorbidities, affected breast side, maximum tumor diameter on ultrasound, maximum pathological tumor diameter, clinical tumor stage, molecular subtype, and disease duration. The operation time, intraoperative blood loss, postoperative drainage volume, and extubation time were recorded and compared between groups. Additionally, the occurrence of early-stage complications (1-3 months after operation; including subcutaneous fluid accumulation, incision infection, superficial skin burns) and late-stage complications (>3 months after operation; including pectoralis major muscle adhesion, changes in breast appearance and shape, sensory discomfort) were assessed. At 6 months after operation, the cosmetic outcome of breast-conserving surgery was rated for all groups. Results The UO group had the shortest operation time, followed by the UI group, LO group, and LI group, showing significant differences between groups (P<0.05). The UO group had the least intraoperative blood loss, followed by the LO group, UI group, and LI group; except for the difference between UO group and LO group, which was not significant (P>0.05), the differences between the other groups were significant (P<0.05). The UO group had the least postoperative drainage volume, followed by the LO group, UI group, and LI group; except for the difference between LO group and UI group, which was not significant (P>0.05), the differences between the other groups were significant (P<0.05). The extubation time of the LI group was significantly longer than that of the other groups (P<0.05). All patients were followed up 4-12 months, with an average of 8 months. And 193 patients were followed up more than 6 months, including 48 patients in UO group, 47 in LO group, 49 in UI group, and 49 in LI group. In the early-stage period, the LI group had a higher incidence of subcutaneous fluid accumulation after tube removal compared to the UO group and LO group (P<0.05), while there was no significant difference in the incidences of other early complications between groups (P>0.05). In the late-stage period, the LI group had significantly higher incidences of pectoralis major muscle adhesion and changes in breast appearance and shape than UO group and LO group (P<0.05), and a significantly higher incidence of sensory discomfort than UO group (P<0.05). There was no significant difference in the incidences of other late-stage complications between groups (P>0.05). At 6 months after operation, the cosmetic outcomes of breast-conserving surgery were significantly better in UO group, LO group, and UI group than in LI group (P<0.05); there was no significant difference between the other groups (P>0.05). Conclusion In the treatment of early-stage breast cancer using SMPSL-BCS, patients with tumors located in the upper outer quadrant show the best effectiveness. The effectivenesses are similar for patients with tumors in the lower outer and upper inner quadrants. However, patients with tumors in the lower inner quadrant do not experience significant advantages. Therefore, it is recommended that SMPSL-BCS should not be the first-choice surgical method for patients with tumors in the lower inner quadrant.