The clinical significance of NK-like T CD3+/CD16+CD56+ cells in chronic lymphocytic leukemia (CLL) is still a subject of controversy. There are few previous descriptions that this cell population can be qualitatively or quantitatively deficient in CLL patients. In the present study we investigated the clinical value of CD3+/CD16+ CD56+ cells as predictors of disease progression. We assessed the frequencies of CD3+/CD16+CD56+ cells by the flow cytometry in a group of 300 CLL patients. The percentage of CD3+/CD16+CD56+ cell population expressed as the percentage of CD3+ lymphocyte compartment showed an inverse correlation with ZAP-70 and CD38. Additionally, the CD3+/CD16+CD56+ showed an inverse correlation with LPL/ADAM29 ratio. Likewise, the ability of these cells to cytokine expression correlated with ZAP-70 expression. A positive correlation between percentage CD3+/CD16+CD56+ cells and TFS was found. The decreased percentage of these cells was associated with higher death risk in CLL patients. Furthermore, the percentage of CD3+/CD16+CD56+ cells was significantly decreased in patients who showed progression of disease. This study suggests that assessment of CD3+/CD16+ CD56+ cells may be helpful in determining a worsening of clinical course. Monitoring of these cell numbers and function may provide useful information for determining disease activity. Especially, it could be intormative to look at these cells in patients with stage 0 CLL. For this patient group immunological control and dysfunction are probably important factors.