It has long been held that the main difference between cranial and trunk neural crest (CNC and TNC, respectively) was the potential of CNC to originate mesenchymal cell types, especially skeletogenic. This is an age-old question that continues to challenge researchers, even today. Unfortunately, to date, no consensus has concluded the extent of TNC mesenchymal potential, nor has a systematic review been conducted to organize current knowledge about this fascinating question. However, the number of studies related to this question have expanded and deepened considerably in the last few years thanks to several new different species of vertebrates employed, the generation of transgenic animal strains, the combination of cell markers, and also the improvement of cell culture conditions through the use of different substrates and signaling molecules. Therefore, this review summarizes the literature showing that TNCCs can generate a broad range of mesenchymal cell types, including skeletogenic. This potential can be unveiled by certain favorable in vitro conditions, but it also seems to be expressed in some animal structures in vivo, to which TNCCs contribute. We also present several works that offer a contrary view and do not detect any mesenchymal/skeletogenic contribution of TNCCs in vivo. Perhaps, it is the controversy itself that makes this subject even more exciting.