Abstract: Autologous fat grafting has become a widely used treatment in breast reconstruction, although there is an ongoing debate about its oncological safety. In fact, we and others have recently shown that all the components of adipose tissue including mature adipocytes and adipose stem cells contribute to breast cancer progression, results that will be presented here in addition to preclinical studies addressing the safety of fat grafting in mouse models. At clinical levels, 2 extensive reviews of the literature on the subject have been recently published. Although the procedure appears globally safe, both reviews underlined the lack of studies with matched control group and long-term follow-up to provide a definitive conclusion. In the only matched cohort study conducted in Milan, we showed that there was no evidence that fat grafting using the standard Coleman techniques significantly increases the risk of breast cancer recurrence. However, this study underlines a potential risk for patients exhibiting in situ carcinoma—a result that we recently confirmed by a dedicated study. To conclude, both preclinical and clinical studies are needed to definitively assess the risk of breast cancer recurrence associated with fat grafting. Two questions that are discussed here appear of importance. Would the results that we obtained with in situ carcinomas be confirmed by other studies? What would be the effect of fat enrichment with adipose stem cells on tumor recurrence?