Analysis of an Ewing sarcoma gene expression dataset (GSE17679; ref. 13) annotated with clinical and survival data revealed that patients with tumors expressing high levels of RNAs for SHMT2 or MTHFD2, which encode two key enzymes involved in the mitochondrial arm of the one-carbon metabolic pathway (Fig. 1A), experience dramatically reduced overall survival, whereas no such association was found for SHMT1. Here, MTHFD2 is linked to Ewing sarcoma.