The hedgehog signal transduction network is a critical mediator of cell-cell communication during embryonic development. Evidence also suggests that properly regulated hedgehog network function is required in some adult organs for stem cell maintenance or renewal. Mutation, or misexpression, of network genes is implicated in the development of several different types of cancer, particularly that of skin, brain, lung, and pancreas. Recent studies in the mouse mammary gland have demonstrated roles for hedgehog network genes at virtually every phase of mammary gland development where it regulates such diverse processes as embryonic mammary gland induction, establishment of ductal histoarchitecture, and functional differentiation in lactation. Further, studies suggest a role for misregulated network function in the progression of breast cancer.