Prognostic assessment of B-cell chronic lymphocytic leukemia (CLL) patients is generally based on either Rai or Binet clinical staging systems. However, new biological parameters which reflect the clinical heterogeneity of disease are under investigation. Cellular and molecular features including tumor cell proliferation, immunophenotype, adhesion molecules expression and release, karyotypic abnormalities and biological findings of increased angiogenesis have been correlated with tumor mass and survival. It is not clear, however, whether the newly identified prognostic parameters will eventually replace clinical variables representative of tumor mass. More likely, biological parameters might be incorporated into clinico-prognostic models thus leading to the formulation of a clinico-biological system for CLL.