W. Kimryn Rathmell, Chad Creighton and colleagues report the genomic analysis of 66 chromophobe renal cell carcinomas (ChRCCs), which constitute a rare subtype of kidney cancer, and matched normal tissue (Cancer Cell 26, 319–330, 2014). The researchers analyzed whole-exome sequence, gene expression profiles and CpG methylation profiles from all 66 tumor-normal pairs, whole-genome sequence from 50 pairs and mitochondrial DNA sequence form 61 pairs. The driver genes TP53 and/or PTEN were found to be significantly mutated in 53% of the samples. Six of the 50 whole genome–sequenced tumors also showed rearrangements involving the TERT promoter, which led to higher levels of TERT expression. Finally, by comparison to available data on clear cell renal cell carcinoma (ccRCC), the authors found that ChRCC and ccRCC have distinct anatomical origins, as reflected in their diverged patterns of gene expression and methylation. ChRCC had increased expression of genes encoding enzymes of the Krebs cycle, whose expression is strongly suppressed in ccRCC. The results indicate that these two related tumor types support tumor growth through different bioenergetics strategies.