Prostate cancer has a range of clinical outcomes, from complete remission in response to treatment to death as a result of aggressive metastasis. Prognosis for individuals with prostate cancer is not readily predictable, and new diagnostics will be useful for treatment strategy determination. In this issue of the JCI, Haffner and colleagues use comprehensive tumor genome sequencing to investigate the origin of genetic mutations underlying a case of lethal prostate cancer. Surprisingly, the lethal clone in this individual arose from a tumor focus that is typically considered very low risk based on histology. Their report highlights the need to collect and curate “N of 1” cases to develop a database that can be used for clinical decision making.