Background B-cell chronic lymphocytic leukemia (B-CLL) is a clinically heterogeneous disease; some patients rapidly progress and die within a few years of diagnosis, whereas others have a long life expectancy with minimal or no treatment. Aim of the study: The aim of this study is to assess the pretreatment levels of CLLU1 in relation to other prognostics markers and to evaluate its impact on the prognosis of CLL patients. Patients and methods: Seventy-three cases of CLL were characterized for CLLU1 level by a semiquantitative RT-PCR. Univariate analysis and correlations were carried out to test the markers’ ability to identify patients at risk and as prognostic markers in the context of established prognostic factors. Results: CLLU1 expression was determined in 42/73 (57.5%) of B-CLL patients. There was a highly significant difference in the age and Binet staging in both CLL patients with positive CLLU1 and negative CLLU1 expression (P < 0.0001 and P= 0.0274, respectively). There was a significant increase in CLLU1 expression in CLL patients with positive CD38 and short lymphocyte doubling time (LDT) (P < 0.001 and P < 0.0044); this significance was not found with high ZAP-70 and b2 microglobulin (B2M) markers. The relative risk of early death with positive CLLU1 was increased with ZAP-70 and LDT (P= 0.0204 and 0.0084) and reduced with CD38 and B2M (P= 0.0787 and 0.0750). The poor clinical outcome was associated with positive CLLU1 and ZAP-70 and LDT (P = 0.0421 and 0.0084, respectively). B-CLL with positive CLLU1 coexpressed with high B2M and/or CD38 had a slower disease progression (P = 0.06 and 0.235, respectively). Conclusion: CLLU1 expression is an important prognostic marker in B-CLL that could potentially be applied to predict outcome in CLL patients. The CLLU1 may be particularly useful in refining the prognosis of CLL patients.