Toll-like receptor 4 (TLR4) is one member of a class of pattern recognition receptors that play a significant role in the physiologic innate immune response. As leukemia is a disease state that may be associated with a compromised immune system, it was hypothesized that depressed TLR4 function resulting from decreased gene expression might be related to the development and further sustained presence of a leukemic clone of cells. This study thus analyzed gene expression of TLR4 in groups of lymphocytic leukemia cases, myeloid leukemia cases, cases of myeloid leukemia in remission, and normal controls by real-time quantitative reverse transcription-PCR (qRT-PCR). It was observed that TLR4 gene expression was indeed decreased to a statistically significant degree (P<0.05) in both the lymphocytic leukemic subset and myeloid leukemic subset when compared to normal controls. Thus, further study is warranted into determining whether this decreased TLR4 expression contributes to the pathogenesis of leukemic clone development through an associated depressed immune surveillance as well as whether TLR4 agonists might serve to effectively strengthen the response of the immune system in battling leukemic burden.