The canonical Wnt signaling pathway is frequently overactivated in several types of human cancer. Defects in different components of the Wnt signaling pathway promote tumorigenesis and tumor progression. Accordingly, the pathway has been intensely studied to understand its importance in cancer biology and as therapeutic target. Recent studies have found that the low-density lipoprotein receptor-related protein (LRP)5 and 6 are essential Wnt coreceptors and interact with several key components of the Wnt signaling pathway. Furthermore, it has been demonstrated that LRP5 and 6 are potential oncogenic proteins. Thus, blockade of LRP56 function may lead to new strategies in cancer treatment.