PURPOSE: After the first subcutaneous mastectomy with nipple preservation in 1974 at the Nottingham Breast Clinic in United Kingdom, many studies have shown that skin-sparing mastectomy (SSM) with the preservation of the nipple-areola complex (NAC) is an oncologically safe procedure with good cosmetic outcomes in selected mastectomy patients. However, the clinical indications for NAC preservation have not yet been precisely defined. This study was performed to investigate the predictive factors for NAC-based neoplastic involvement to determine the indications for NAC preservation. METHODS: A retrospective study of 198 patients with invasive breast cancer who underwent modified radical mastectomy (MRM) at the Department of Surgery at Chonnam University Hospital from April of 2004 to April of 2006 was performed. Patients with bilateral breast cancer were excluded from the study. The predictive factors analyzed for NAC involvement were the hormone receptor status, tumor size, tumor localization, multiplicity, axillary lymph node status, nuclear grade, tumor-nipple distance (TND), and lymphovascular invasion (LVI). RESULTS: The overall frequency of malignant NAC involvement was 19 out of the 198 patients (9.5%) as determined by definitive histology. Significant differences were found for tumor size (P=0.015), axillary lymph node status (P=0.008), TND (P=0.044), and LVI (P=0.014). There were no significant differences for the hormone receptor status, multiplicity, nuclear grade, and localization. CONCLUSION: Although the sample size in this study was small, the findings suggest that the clinical contraindications for NAC preservation should include tumors >2.4 cm, a positive axillary lymph node status, TND <4 cm, and positive LVI. NAC preservation can be offered in selected patients after preoperative or intraoperative evaluation of the tumor size, axillary node status, TND, and LVI.