A national cooperative project on rare paediatric tumours (the TREP project) was launched in 2000 in Italy, with a view to improving the clinical management and the basic research on these 'orphan' tumours, defined as those childhood solid malignancies characterised by an annual incidence <2/million and not considered in other clinical trials. This paper describes the process that the group developed and the problems it had to face, and aims to stimulate a debate on the rationale, scientific relevance and feasibility of running scientific research programs on rare childhood neoplasms. In the first phase of its activity, the project developed diagnostic and therapeutic recommendations for each rare tumour and established a collaborative network between 'experts' dedicated to each histotype and other specialists (i.e. adult oncologists, surgeons) involved in the management of these tumours. From 2000 to 2005, 297 patients have been registered from 35 Italian centres. This experience demonstrates the feasibility of a national multidisciplinary cooperation on rare paediatric malignancies and suggests that international studies could be realised.