The clinical course of patients with chronic lymphocytic leukemia (CLL) is highly heterogeneous. Gene expression analyses have revealed that leukemic cells with unmutated immunoglobulin heavy chain genes (IgV_H) differ from CLL cells with mutated IgV_H in the expression level of some genes, i.e. encoding kinase ZAP-70 and antigen CD38. Recently, additional markers in CLL, including the expression level of apoptosis-regulating genes/proteins (Bcl-2, Mcl-1) and microRNAs, have been suggested. In this review, we attempt to provide data concerning the properties of lipoprotein lipase (LPL), as well as to present its prognostic value in CLL. LPL mRNA expression level was able to predict mutational status in a high percentage of CLL cases and high LPL expression was associated with shorter treatment-free survival. Importantly, since LPL activity is low (or absent) in other blood cell types, its expression can be determined by PCR technique in peripheral blood mononuclear cells or in lysed blood samples.