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Cancer of the bladder shows divergent clinical behaviour following diagnosis and it has been proposed that two major groups of tumours exist that develop via different molecular pathways. Low-grade, non-invasive papillary tumours recur frequently, but patients with these tumours do not often suffer progression of disease to muscle invasion. In contrast, tumours that are invading muscle at diagnosis are aggressive and associated with significant mortality. Molecular studies have identified distinct genetic, epigenetic and expression changes in these groups. However, it is not yet clear whether there is direct progression of low-grade superficial tumours to become invasive (a Jeckell and Hyde scenario) or whether in those patients who apparently progress from one form of the disease to the other, different tumour clones are involved and that the two tumour groups are mutually exclusive (‘chalk and cheese’). If …