CD38 was suggested to be not only a prognostic marker but also a key element in the pathogenetic network underlying chronic lymphocytic leukemia (CLL). We aimed at determining whether polymorphisms of CD38 gene influence the risk of B-CLL and thus analyzed two potentially functional CD38 single nucleotide polymorphisms (SNPs), rs6449182 (184 C>G), and rs1800561 (418 C>T) using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)-based assays in a study including 70 B-CLL patients and 70 age- and gender-matched controls. Our results demonstrated that the homozygous mutant genotypes of the two studied SNPs (GG and TT) showed a significantly higher risk of B-CLL compared with the homozygous wild types (p value G) and rs1800561 (418 C>T)].