Despite the inherent osteogenic differentiation potential of osteosarcoma [1–4], the low expression levels of osteogenic markers, such as RUNX2 (RUNX family transcription factor 2), OCN (osteocalcin), and OPN (osteopontin), observed in numerous human osteosarcoma cell lines suggest that osteogenic differentiation defects are a prevalent characteristic of osteosarcoma [17, 18]. The gene discussed is SPP1; the disease is osteosarcoma.