Cancer research has benefited immensely from the use of animal models. Several genetic tools accessible in rodent models have provided valuable insight into cellular and molecular mechanisms linked to cancer development or metastasis and various lines are available. However, at the same time, it is important to accompany these findings with those from alternative or non-model animals to offer new perspectives into the understanding of tumor development, prevention, and treatment. In this review, we first discuss animals characterized by little or no tumor development. Cancer incidence in small animals, such as the naked mole rat, blind mole rat and bats have been reported as almost negligible and tumor development may be inhibited by increased defense and repair mechanisms, altered cell cycle signaling and reduced rates of cell migration to avoid tumor microenvironments. On the other end of the size spectrum, large animals such as elephants and whales also appear to have low overall cancer rates, possibly due to gene replicates that are involved in apoptosis and therefore can inhibit uncontrolled cell cycle progression. While it is important to determine the mechanisms that lead to cancer protection in these animals, we can also take advantage of other animals that are highly susceptible to cancer, especially those which develop tumors similar to humans, such as carnivores or poultry. The use of such animals does not require the transplantation of malignant cancer cells or use of oncogenic substances as they spontaneously develop tumors of similar presentation and pathophysiology to those found in humans. For example, some tumor suppressor genes are highly conserved between humans and domestic species, and various tumors develop in similar ways or because of a common environment. These animals are therefore of great interest for broadening perspectives and techniques and for gathering information on the tumor mechanisms of certain types of cancer. Here we present a detailed review of alternative and/or non-model vertebrates, that can be used at different levels of cancer research to open new perspectives and fields of action.