Using a cut-off figure of 15 new cases/100,000 population/year as a definition for rare cancers, it appears that these tumors account for up to 25% of incident cases in the USA (1). With a more rigorous criterion of less than 6/100,000, the figure is much less, but it appears that outcomes are worse than for common cancers (2). There is also masking of some rare situations (viz. uncommon presentations of common cancers – e.g. small cell anaplastic cancers of bladder or prostate) (3,4). Key items in a structured approach include histological review by an expert tumor pathologist, clinical review of purported unusual imaging or other diagnostic results, careful literature review from expert sources, referral to a centre of excellence for a second opinion from a published expert, and development of a management partnership with that expert. In an evolving era of molecular diagnostics, gene expression analyses may add clarity to the precision of diagnosis and may provide therapeutic targets in uncommon cancers. Much caution should be exercised when relying upon isolated case reports and literature reviews, which may involve data dredging and recycling, unconfirmed pathological diagnoses, editorial bias against negative reporting and production by the most inexperienced clinicians. Examples of structured approaches to management of collecting duct cancer and medullary carcinoma of kidney (3-6), and small cell anaplastic bladder cancer are reviewed as illustrations of a structured approach.