Sciacovelli et al. find that the higher levels of intracellular fumarate that result from loss of fumarate hydratase (FH), which causes hereditary leiomyomatosis and renal cell carcinoma (HLRCC), promotes epithelial-to-mesenchymal transition (EMT). Fumarate inhibits tet methylcytosine dioxygenase (TET) family enzymes, and the authors found that in FH-null cells and wild-type cells supplemented with fumarate, TET-mediated demethylation of the microRNA (miRNA) cluster mir-200ba429 was inhibited, allowing expression of EMT transcription factors targeted by these miRNAs. Loss of FH was also associated with an EMT signature and poor outcomes in human HLRCC and papillary renal-cell carcinomas lacking FH.