The clustering of specific cancers in breeds and families suggests that there may be a genetic component in the development of the disease.

The investigation of cancer susceptibility in families or breeds of dogs is of critical importance to dog breeders and dog owners alike. Unlike other heritable conditions, genetic susceptibility to cancer may not manifest in disease until a dog has reached middle age, and long after it has achieved breeding potential. When present, this genetic susceptibility is most likely to be due to a process called loss of heterozygosity. Individuals inherit 2 copies of each gene upon conception; one from the sire, and one from the dam. Each of these gene copies is called an "allele." A family or a breed may have, through the course of time, lost a functional allele of a "tumor suppressor gene" through mutation. The affected individuals are heterozygous (that is, they have two different alleles, and only one is functional). These individuals will not develop disease (cancer), unless the second, functional copy of the "tumor suppressor gene" in question is mutated in a cell that retains the capacity to divide; for example, white blood cells that undergo division as they fight infections, pigment-producing cells that divide as a response to insult or injury to the skin, or bone cells that undergo division in the process of bone remodeling.