In December 2000, the Italian Registry of Laparoscopic Surgery of the Spleen (IRLSS) was formally launched under the auspices of the Italian Society for Endoscopic Surgery and New Technologies (SICE). The aim of this multicentre study was to analyse various aspects of the treatment that are still under discussion, such as the extension of the laparoscopic indications in cases of malignancy, independently of the associated splenomegaly, patient selection and operative techniques. A retrospective review of 379 patients undergoing laparoscopic splenectomy for haematological diseases from February 1, 1993, to September 15, 2005, was conducted. Data were collected from the 18 italian centres participating in the IRLSS. The mean length of surgery was 140 minutes (range: 25-420). Conversion was necessary in 25 cases (6.6%), and at least one accessory spleen was found in 30 patients (8%). The mean spleen weight was 1200 g (range: 85-4500). Perioperative death occurred in two cases (0.5%). There were no complications in 312 patients (82.3%), with a mean hospital stay of 5.5 days (range: 2-30). Morbidity occurred in 67 patients (17.8%), mainly consisting in transient fever (n = 22), pleural effusions (n = 16), and actual or suspected haemorrhage (n = 14), requiring re-intervention in 7 patients. This first study carried out on the IRLSS data shows that laparoscopic splenectomy may constitute the gold standard for haematological diseases with a normal-sized spleen. The low morbidity and mortality rates suggest that laparoscopic splenectomy can be successfully proposed also for splenomegaly in haematological malignancies.