Rare cancers represent a major diagnostic as well as therapeutic global challenge. All together they account for approximately 20% of all cancers and, in consideration of the lack of expertise, they represent a major source of discrimination among patients. More than 500,000 people in the European Union are diagnosed with a rare cancer every year. They affect more than 4 million people in the European Union. The definition of rare cancers has been source of sharp debate through the last decades. In the attempt to equate cancers to rare diseases in the past has predominated an approach based on prevalence. It is however intuitive that cancer in general represents an “acute” disease, and therefore is hardly comparable with a rare genetic conditions leading for example to a chronic metabolic disorder. An extensive work undertaken by the EU funded Surveillance of Rare Cancers in Europe (RARECARE) project. has generated the idea that rare cancers should be defined on the basis of incidence. The meta-analysis of the dataset of the European cancer registries has offered a detailed view of the incidence of rare cancers. On the basis the clinical/therapeutic relevance a threshold for rarity has been set. Rarity is currently defined whenever the incidence is below 6 cases/100.000/year. A total of 186 cancer types have been defined as rare, and the estimated annual incidence rate of all rare cancers in Europe is about 108 per 100,000, corresponding to 541,000 new diagnoses annually or 22% of all cancer diagnoses. Five-year relative survival was on average worse for rare cancers (47%) than common cancers (65%). About 4,300,000 patients are living today in the European Union with a diagnosis of a rare cancer, 24% of the total cancer prevalence. Centers of excellence for rare cancers or groups of rare cancers could provide the necessary organisational structure and critical mass for carrying out clinical trials and developing alternative approaches to clinical experimentation for these cancers.