Autologous fat grafting is the gold standard for soft tissue repair. The donor fat depot is chosen where a surplus of subcutaneous fat is found. However, the adipose tissues from different parts of the body are not equivalent. Despite the heterogeneity in fat depots, it is still considered that any adipose tissue site is a suitable fat depot donor for transplantation. Matching embryonic origins and Hox code between transplanted stem cells and the host microenvironment emerges as a critical parameter to achieve correct repair in different preclinical models. It has also recently been reported that the individual fat depots routinely used in reconstructive surgery exhibit distinct embryonic origins and express different HOX code. An opposite gradient from the upper to the lower body exists between expressions of HOXC10 and the neural crest marker PAX3. This observation raises the question of the choice for the best fat donor site. Matching between the host tissue and the donor fat sites is a factor that urgently deserves consideration to improve postoperative outcomes and safety of autologous fat grafting.