Interestingly, we successfully induced early stages of ferroptosis in a panel of three human osteosarcoma cell lines, as confirmed by the prompt and significant upregulation of specific markers, such as PTGS2 and SLC7A11, in response to exposure to RSL3, while the execution of the process was highly heterogeneous, indicating the activation of signaling pathways conferring resistance. This evidence concerns the gene SLC7A11 and osteosarcoma.