Expanding the potential target population for FEN1 inhibition, screening of cell line panels reveals a specific dependency of Ewing sarcoma (EWS) cells on FEN1 activity, driven by elevated expression of SLFN11, a transcriptional target of the EWS–FLI gene fusion, and a potential population biomarker for FEN1 inhibition. The gene discussed is SLFN11; the disease is Ewing sarcoma.