Nipple-sparing mastectomy (NSM) is an increasingly utilized surgical option in managing breast carcinoma; however, data on malignant involvement of a separately submitted nipple margin are scant. Consecutive NSM, including those performed for therapeutic and prophylactic purposes, over a 4-year period (2007–2011), were studied. A separately submitted nipple margin was evaluated by permanent H&E preparations and via frozen section evaluation whenever requested. 325 consecutive NSM specimens, 208 (64%) therapeutic-NSM, and 117 (36%) prophylactic-NSM were studied. All nipples were clinically unremarkable. 86% (179/208) of nipple margins from therapeutic-NSM and 100% (117/117) from prophylactic-NSM showed no histopathologic abnormality. 14% (29/208) of nipple margins from therapeutic-NSM and no nipple margin from prophylactic-NSM showed malignancy. Frozen section evaluation was performed in 188/325 NSM (58%) with a sensitivity of 64% and specificity of 99%. Central tumor location and stage N2/N3 lymph node status were significantly associated with nipple margin positivity (χ2 ≤ 0.05). Subsequent nipple resection was performed in 69% (20/29) of nipple margin-positive cases with residual malignancy found in 40% (8/20, including three cases of invasive carcinoma). In a mean follow-up of 33 months, one invasive carcinoma recurred in the “saved” nipple, 36 months after therapeutic-NSM. 14% (29/208) of nipple margins in therapeutic-NSM and no nipple margin (0/117) in prophylactic-NSM showed malignancy. Central tumor location and N2/N3 stage were significantly associated with nipple margin positivity (χ2 ≤ 0.05).