Metastasis suppressors are genes/proteins involved in regulation of one or more steps of the metastatic cascade while having little or no effect on tumor growth. The list of putative metastasis suppressors is constantly increasing although thorough understanding of their biochemical mechanism(s) and evolutionary history is still lacking. Little is known about tumor-related genes in invertebrates, especially non-bilaterians and unicellular relatives of animals. However, in the last few years we have been witnessing a growing interest in this subject since it has been shown that many disease-related genes are already present in simple non-bilateral animals and even in their unicellular relatives. Studying human diseases using simpler organisms that may better represent the ancestral conditions in which the specific disease-related genes appeared could provide better understanding of how those genes function. This review represents a compilation of published literature and our bioinformatics analysis to gain a general insight into the evolutionary history of metastasis-suppressor genes in animals (Metazoa). Our survey suggests that metastasis-suppressor genes emerged in three different periods in the evolution of Metazoa: before the origin of metazoans, with the emergence of first animals and at the origin of vertebrates.