Wnt proteins, derived from the names of two genes; Drosophila Wingless (Wg) and the mouse Int-1 genes, This novel family of proteins are intimately involved in cellular signaling pathways that play a role in a variety of processes that involve embryonic cell patterning, proliferation, differentiation, orientation, adhesion, survival, and apoptosis.Several secreted protein families antagonize or modulate Wnt/β-catenin signaling, two of the most important antagonists are SFRP1and DKK3.Functional loss of Wnt antagonists by promoter hypermethylation can contribute to activation of the Wnt pathway and results in carcinogenesis.This study aimed to assess the role and the frequency of epigenetic silencing of the Wnt antagonists SFRP1 and DKK3 by promoter hypermethylation in B-ALL and AML patients by a method of methylation specific PCR. Results: we found a significantly higher frequency of methylation in B-ALL and AML compared to control. SFRP1 and DKK3 silencing, by promoter hypermethylation, is an early and a common event in the evolution of acute leukemia.Patients with aberrant methylation phenotype may benefit from treatment with demethylating agents as this line of management expected to damp down the Wnt signaling activity and hence the activity of the disease. This study also offers a preliminary basis for further studies to monitor hypermethylation of Wnt antagonists as a marker for minimal residual disease.