OBJECTIVES: Orphan drugs (OD) constitute a class of drugs that have been developed specifically to treat a rare medical condition referred to as “rare disease”. In January 1983, the United States (US) implemented the Orphan Drug Act (ODA). The European orphan drugs regulation was implemented almost 20 years after the US regulation, in 16 December 1999. Our objective is to compare the number of oncology orphan drugs designated and approved in the European Union (EU) and US. METHODS: All designated OD were extracted from US FDA database and the European Medicines Agency (EMA) database. The oncology condition was selected in the 2 lists. Drugs with withdrawn orphan designation or market authorisation were excluded from the analysis. Different orphan designations granted for different indications for the same molecule were considered separate approvals. Then the numbers of designations and approvals by period of time were compared between EU and US. RESULTS: In the US, 969 oncology drugs were orphan designated between 1984 and 2015, of which 122 are approved (12.59%). In EU between 2000 and 2015, 397 oncology products received OD designation of which 35 (8.81%) were approved. During the same period 823 where designated in US and 77 (9.35%) approved. Proportion of approvals was similar. Trends showed continuous sustained growth overtime in US for designation and approval. In EU after an initial catch up period (2000-2005) the growth was less marked. CONCLUSIONS: This analysis supports the continuous gap between US and EU in the number of designated and approved oncology products, despite much longer data protection offered in EU. The difference is more driven by entrepreneurial attitude (more products filled and developed) in US than by the regulatory criteria for designation that are reasonably aligned or by the highest rejection rate in EU.