Several reasons may account for this delayed translational application of preclinically developed compounds to a robust clinical testing, namely, technical issues concerning the isolation of the rare CSCs, difficulties in identifying specific surface markers that can substantiate the stem cell-like phenotype in osteosarcoma (for instance, CD133, CD29, CD90, CD105, CD44, ICAM-1, CD56, CD117, CBX3/ABCA5, CD248, CD271, CD49b, and CD24 are also expressed by several other tumors) and the histological validation in patient clinical samples, as we previously extensively discussed [8]. This evidence concerns the gene ENG and osteosarcoma.