To analyze clinical and laboratory features at presentation in correlation to treatment response and overall survival; evaluation of different treatment approaches.The data of 151 consecutive HCL patients observed between 1982 and 2005 were retrospectively analyzed.The following data at presentation were analyzed and compared to response, DFS, PFS and OS: Hb 10,000/microl (15%); Splenomegaly (75%); Bone marrow involvement > 70% (27%). At univariate analysis only WBC > 10,000/microl resulted significantly correlated to reduced PFS. 88 Pts received as first line treatment alpha2-interferon (IFN) alone, 49 purine analogues (PA) alone or in combination with IFN, 5 were treated with splenectomy. Among IFN treated patients CR, PR and SD were obtained in 21.6%, 73.8%, 4.5% respectively of the patients; while among PA treated patients in: 26.5%, 71.4%, 2.0% respectively. DFS was significantly prolonged in patients treated with PA with respect to IFN. No significant difference in OS was observed. Median PFS was 27.6 months, median OS is projected at 238 months after a median follow up of 131 months.Among the routine clinical and hematochemical baseline features only the presence of WBC > 10,000/microl was correlated to a lower PFS. First line treatment with purine analogues is correlated to prolonged PFS and DFS with respect to IFN; nevertheless no difference is observed in OS.