The RARECARE list was hierarchically organised into three tiers. The first tier is based on patient referral purposes, i.e. it is relevant under the health-care organisation perspective. The second tier groups provide a list of cancer entities distinct with respect to clinical management and clinical research targets. The third tier includes all pathologically distinct entities defined by the WHO blue book entities. An example of this organisation is reported in Table 2.

As a final step, RARECARE defined rare cancers as those with an incidence of <6/100,000/year, corresponding to <30,000 new cases/year in Europe. A total of about 200 cancers were recognised as rare according to this definition.

In Europe rare cancers are officially defined according to the prevalence criterion (<50/100,000), in the same way as rare diseases in general. However, prevalence has shortcomings as a measure of cancer rarity since some cancers with low incidence but good survival fall into the common cancer category as good survival pushes up prevalence; examples are squamous cell carcinoma of the uterine cervix and thyroid carcinoma. Similarly, some commonly occurring diseases for which survival is poor are considered rare because poor survival pushes prevalence down. Examples are adenocarcinoma of the stomach and lung and squamous cell carcinoma of the lung. These considerations suggest that incidence is better for defining rare cancers and is also in harmony with the sub-acute clinical course of most rare cancers, whereas most rare non-neoplastic diseases have a chronic course better measured by prevalence indicator. The RARECARE rarity threshold at <6/100,000 is of course arbitrary and was selected by pragmatic considerations. For example, a lower threshold of <3/100,000/year would be considered as common epithelial cancers of the oral cavity and lip, epithelial cancer of the oropharynx, epithelial cancers of the larynx, epithelial tumour of the gallbladder, soft tissue sarcomas, tumours of the testis and paratestis, carcinomas of the thyroid tumour of central nervous system, neuroendocrine tumours, myeloproliferative neoplasms and acute myeloid leukaemia. Yet these forms present all the characteristics of rare cancers, being often inadequately diagnosed and treated in relation both to lack of knowledge and lack of clinical expertise, clinical trials are rarely performed. They are best treated in specialised centres. Thus, the <6/100,000 threshold was selected to include all the forms with the problems typically present in rare cancers.