BACKGROUND: In 2005, the government of Lombardy, an Italian region with an ethnically varied population of approximately 9.8 million inhabitants including 250,000 blood donors, founded the Lombardy Rare Donor Programme, a regional network of 15 blood transfusion departments coordinated by the Immunohaematology Reference Laboratory of the Ca' Granda Ospedale Maggiore Policlinico in Milan. During 2005 to 2012, Lombardy funded LORD-P with 14.1 million euros. MATERIALS AND METHODS: During 2005-2012 the Lombardy Rare Donor Programme members developed a registry of blood donors and a bank of red blood cell units with either rare blood group phenotypes or IgA deficiency. To do this, the Immunohaematology Reference Laboratory performed extensive serological and molecular red blood cell typing in 59,738 group O or A, Rh CCDee, ccdee, ccDEE, ccDee, K- or k- donors aged 18-55 with a record of two or more blood donations, including both Caucasians and ethnic minorities. In parallel, the Immunohaematology Reference Laboratory implemented a 24/7 service of consultation, testing and distribution of rare units for anticipated or emergent transfusion needs in patients developing complex red blood cell alloimmunisation and lacking local compatible red blood cell or showing IgA deficiency. RESULTS: Red blood cell typing identified 8,747, 538 and 33 donors rare for a combination of common antigens, negative for high-frequency antigens and with a rare Rh phenotype, respectively. In June 2012, the Lombardy Rare Donor Programme frozen inventory included 1,157 red blood cell units. From March 2010 to June 2012 one IgA-deficient donor was detected among 1,941 screened donors and IgA deficiency was confirmed in four previously identified donors. From 2005 to June 2012, the Immunohaematology Reference Laboratory provided 281 complex red blood cell alloimmunisation consultations and distributed 8,008 Lombardy Rare Donor Programme red blood cell units within and outside the region, which were transfused to 2,365 patients with no untoward effects. DISCUSSION: Lombardy Rare Donor Programme, which recently joined the ISBT Working Party on Rare Donors, contributed to increase blood transfusion safety and efficacy inside and outside Lombardy.