However, in contrast to ccRCC, where HIF accumulation is primarily due to VHL inactivation (Foster et al. 1994; Gnarra et al. 1994; Mandriota et al. 2002; Semenza 2012b; Gossage, Eisen, and Maher 2015), or to FH‐ and SDH‐deficient RCC, where HIF is stabilized by oncometabolite accumulation, our findings indicate that HIF upregulation in TFE3‐RCC takes place at the transcriptional level, revealing a unique mode of HIF activation in this RCC subtype. The gene discussed is VHL; the disease is renal cell carcinoma.