The Wnt pathway has been shown recently, to be activated in patients with chronic lymphocytic leukemia (CLL). This is the first study to examine the role of Wnt inhibitory factor-1 (Wif-1) methylation in the pathogenesis of haematolymphoid malignancies. Wif-1, a putative tumor suppressor, is a soluble negative regulator of the Wnt pathway activated in CLL. We studied the role of methylation of Wif-1 in 43 Chinese patients with CLL. At diagnosis, Wif-1 methylation was detected in 5/43 (11.6%) CLL marrow samples. Wif-1 methylation occurred more frequently in patients with advanced age (p = 0.059) but there was no correlation between Wif-1 methylation and sex, lymphocyte count and Rai stage at diagnosis. In conclusion, Wif-1 is infrequently methylated in CLL. Other factors leading to activation of the Wnt pathway warrant further study.