Human breast tumors contain DNA sequences with high homology to the Mouse Mammary Tumor Virus (MMTV) env gene. env encodes the membrane glycoprotein that binds to the MMTV receptor (Mtvr) in mouse tissues and is required for infection. If humans become infected with MMTV, identification of a human Mtvr might shed light on the mechanism of infection. Here, we identified two human genes, Mtvr1 and Mtvr2, encoding proteins highly related to the mouse receptor. Mtvr-related sequences were also detected in other mammalian species. Thus, zoonotic transmission of MMTV is a real possibility given the existence of highly homologous MMTV receptors.