Cells have elaborate machinery to preserve the integrity of their genomes, which nevertheless relentlessly gather new mutations over time. Recent technical advances have enabled high-resolution delineation of these accumulated mutations and their spatial organization in tissues (1–8). It is now possible to deduce which mutations in which genes allowed cells to outcompete their neighbors and colonize nearby regions of normal tissue (clonal expansion). One can also sometimes ascertain which endogenous mutational processes or external mutagens caused these somatic mutations. These recent findings have profound implications for understanding aging and the early stages of cancer initiation. On pages 75 and 82 of this issue, Lawson et al. (9) and Li et al. (10), respectively, delve into the somatic mutations lurking in the normal urothelium—the lining of the bladder and ureter—and relate them to cancers in these tissues.