Zhang et al. examined genetic predisposition to cancer by carrying out whole-exome and whole-genome sequencing of 1,120 patients with cancer who were less than 20 years old. They analysed the sequences of 565 genes that are known to be associated with cancer and were able to identify mutations that were considered to be at least 'probably pathogenic' in only 8.5% of the cohort. It is surprising that the genetic alteration that predisposed these patients to cancer at such a young age could be identified in so few, demonstrating that we have much more to learn.