Background and Objectives. Mastectomy skin flaps (MSF) necrosis is one of the most relevant complications following mastectomies with immediate breast reconstruction. The study evaluates a possible correlation between MSF qualitative and quantitative perfusion grade, using ICG angiography, and skin necrosis. Methods. Consecutive women scheduled for nipple/skin-sparing/skin-reducing mastectomy between May 2020 and April 2021 were prospectively enrolled. Patients were divided into Group 1 in the absence of superficial and full-thickness necrosis (SN; FTN) and Group 2 in the presence of both. T1 (time between ICG injection and the initial perfusion of the least perfused MSF area), ICG-Q1, and ICG-Q% (absolute and relative perfusion values of the least vascularized area) were collected. Results. 38 breasts were considered. FTN was reported in 4 breasts (10.5%) and SN in 3 (7.9%). The two groups statistically differ in T1 (Group2 > Group1) and ICG-Q% (Group1 > Group2) ( p < 0.05). T1 could statistically predict ICG-Q1 and ICG-Q%. Both quantitative values have a sensitivity of 57% and a NPV of 89%; ICG-Q% shows higher specificity (81% vs 77%) and PPV (40% vs 36%). Conclusions. Quantitative ICG angiography may additionally reduce MSF necrosis. Moreover, longer T1 may indicate possible postoperative necrosis. Considering these factors, intraoperative changes of reconstructive strategy could be adopted to reduce reconstructive failure.