BACKGROUND The aim of this study was to evaluate the incidence of CD38 expression in all CLL patients of our institution and to determine its prognostic significance in correlation with other parameters of the disease. PATIENTS AND METHODS We analyzed the CD38 expression in 102 B-CLL patients referred to our department over a period of 12 months. RESULTS The follow-up period ranged from 0 to 18 years. 30 patients (29%) were CD38-positive (CD38+) and 72 patients (71%) were CD38-negative (CD38-) with a median age of 65 and 64 years, respectively. Of the Binet A patients (77), 25% showed an expression of CD38; in Binet B/C patients (25), 67% expressed CD38. Median survival of the CD38- group was 77.5 months and of the CD38+ group 56.3 months. CD38 expression was associated with shorter lymphocyte doubling time (p < 0.0001), a more advanced stage of the disease, and a shorter therapy- and progression-free time (p < 0.0017/p < 0.0012), which was also true in the Binet A subgroup. In 2 cases, we detected a shift from the CD38- to the CD38+ phenotype. CONCLUSION We found a low incidence of CD38+ CLL patients, and CD38 expression predicted significantly a more advanced stage of the disease, shorter lymphocyte doubling time and shorter therapy- and progression-free time.