Nipple-sparing mastectomy (NSM) is increasingly offered to patients undergoing treatment of breast cancer and prophylaxis treatment for reduction of breast cancer risk. NSM is considered oncologically safe for appropriately selected patients and is associated with improved cosmetic outcomes and quality of life. Accepted indications for NSM have expanded in recent years, and currently only inflammatory breast cancer or malignancy involving the nipple is considered an absolute contraindication. Neoplasms close to and involving the nipple areolar complex are common, and cancer of the lactiferous ducts can spread to the nipple. Therefore, accurate determination of nipple involvement at imaging examinations is critical to identifying appropriate candidates for NSM and preventing local recurrence. Multiple imaging features have been described as predictors of nipple involvement, with tumor to nipple distance, enhancement between the index malignancy and the nipple, and nipple retraction demonstrating the highest predictive values. These features can be assessed at multimodality breast imaging, particularly at breast MRI, which demonstrates high specificity and negative predictive value for determining nipple involvement in malignancy. Online supplemental material is available for this article. ©RSNA, 2022.