Rare cancers are malignant tumors with an incidence lower than 6/100,000/year at the EU level. Even if more conservative in comparison to the definition used for rare diseases (also from the regulatory point of view), rare cancers defined this way make up more than twenty percent of new cases of malignant tumors in the EU, including Italy. The rarity of a tumor implies that clinical decision-making is more problematic outside reference centers and networks, that available evidence suffers from a higher uncertainty, that organization of health care is more difficult. In 2019, a Joint Action on rare cancers launched by the European Union, run in parallel to a Joint Action on rare diseases, worked out ten categories of recommendations, among which some on the methodology of clinical research and regulatory aspects. In general, it stressed the value of collaborative clinical networks (at the EU level and, more importantly, nationally) around centers of expertise. Working according to a "hub-and-spoke" logic, these networks can improve quality of care while rationalizing health migration. Regarding the regulatory aspects and more in general to the definition of the state of art, in rare cancers the magnitude of clinical benefit should be the same as for common conditions, but the quality of evidence should be accepted to be less stringent in terms of statistical precision. Otherwise, rare cancer patients would be discriminated against in their access to innovative diagnostic and therapeutic options, even when available. Specifically, orphan drugs can suffer from lower interest of pharmaceutical industry. This justifies some privileges they are granted, among which the 10-year market exclusivity is crucial. However, a critical aspect is the perception of the regulatory risk by the industry. This problem could be limited by closer cooperation between regulatory bodies and rare cancer communities and by flexible regulatory mechanisms, in particular in partnership with clinical networks. In Italy, more constructive interpretations of the rules about the compassionate use of drugs, an even application of Law 648 and the future implementation of the new Law on Rare Diseases could help. In general, refining the methodology of clinical research in small samples would be fundamental.