Invariant NKT (iNKT) cells are CD1d-restricted T cells which express invariant T-cell receptor (TCR) incorporating V24 chain paired with V11 chain and NK cell markers. Human V24+NKT cells play crucial roles in various immune responses including autoimmune and antitumor responses. Little is known however about the role of iNKT in patients with CLL. We investigated iNKT cells numbers in peripheral blood of 60 untreated patients with CLL and 20 healthy individuals matched for age. Analysis of V24 surface expression on CD3+ T cells revealed significantly lower median percentage of iNKT cells in peripheral blood of CLL patients than in healthy donors. Moreover iNKT percentages decrease along with disease progression, and adversely correlate with negative prognostic factors. These results suggest an important role of iNKT cells in the development and progression of CLL, as well as their potential prognostic significance.