The putative existence of a cancer stem cell niche consisting of bi-directional stromal and stem cell secreting factors that trigger cancer stem cell growth and proliferation has been hypothesized in the nervous and hematopoietic systems. In light of this theory, it has been proposed that embryonic stem cell microenvironments, upon interactions with cancer stem cells, may reprogram cancer cells resulting in a substantial inhibition of tumor cell properties. Here, we discuss emerging data that support this novel concept of cancer inhibitory factors produced in the context of embryonic microenvironments as well as by embryonic stem cells (ESCs).