BACKGROUND Rare diseases (RDs) are a heterogeneous group of pathologies, which, when present in a donor, with their anatomic or functional deficiencies, may put the recipient at risk. The aim of our work is to analyze the incidence of RDs in our donors to support transplant experts in the evaluation of these organs. METHODS We retrospectively assessed the incidence of RDs in donors from July 2017 to June 2019, along with the risk attributed, the number of transplanted organs, and the follow-up results of the recipients. RESULTS Over a 24-month period, we had 19 donors with RDs. Of those, the organs of 4 donors were rejected before the risk assessment, the organs of 4 other donors were deemed an unacceptable risk, the organs of 4 more donors were rejected by transplant centers, and the organs of 7 donors were accepted with 16 organs ultimately transplanted (2 hearts, 3 livers, and 11 kidneys). Three of the recipients died of causes not related to the RDs. Thirteen of the recipients are still alive with a functioning organ with an average follow-up of 9 months. CONCLUSIONS Although the evaluation of the results is influenced by the limited follow-up period, the use of donors with RDs has proved safe. One of the critical issues encountered in the evaluation process was the impossibility of carrying out genetic and histologic investigations for each organ in urgency. Moreover, the heterogeneity of RDs and the lack of solid literature data require, for the purpose of assessing the level of risk, a specific assessment of individual cases. To overcome these limitations, a group of experts was set up at the Superior Health Council, who drafted a reference document, which allowed for the assessment of the suitability and risk level of donors with the most frequent RDs.