Paleopolyploidy is the result of genome duplications which occurred at least several million years ago (MYA). Such an event could either double the genome of a single species (autopolyploidy) or combine those of two species (allopolyploidy). Because of functional redundancy, genes are rapidly silenced or lost from the duplicated genomes. Most paleopolyploids, through evolutionary time, have lost their polyploid status through a process called diploidization, and are currently considered diploids e.g. baker's yeast, "Arabidopsis thaliana", and perhaps humans.

Paleopolyploidy is extensively studied in plant lineages. It has been found that almost all flowering plants have undergone at least one round of genome duplication at some point during their evolutionary history. Ancient genome duplications are also found in the early ancestor of vertebrates (which includes the human lineage) and another near the origin of the bony fishes. Evidence suggests that baker's yeast ("Saccharomyces cerevisiae"), which has a compact genome, experienced polyploidization during its evolutionary history.

The term "mesopolyploid" is sometimes used for species that have undergone whole genome multiplication events (whole genome duplication, whole genome triplification, etc.) in more recent history, such as within the last 17 million years.

Polyploid cells and organisms are those containing more than two paired (homologous) sets of chromosomes. Most species whose cells have nuclei (Eukaryotes) are diploid, meaning they have two sets of chromosomes—one set inherited from each parent. However, polyploidy is found in some organisms and is especially common in plants. In addition, polyploidy occurs in some tissues of animals that are otherwise diploid, such as human muscle tissues. This is known as endopolyploidy. Species whose cells do not have nuclei, that is, Prokaryotes, may be polyploid organisms, as seen in the large bacterium "Epulopiscium fishelsoni" . Hence ploidy is defined with respect to a cell. Most eukaryotes have diploid somatic cells, but produce haploid gametes (eggs and sperm) by meiosis. A monoploid has only one set of chromosomes, and the term is usually only applied to cells or organisms that are normally diploid. Male bees and other Hymenoptera, for example, are monoploid. Unlike animals, plants and multicellular algae have life cycles with two alternating multicellular generations. The gametophyte generation is haploid, and produces gametes by mitosis, the sporophyte generation is diploid and produces spores by meiosis.

Polyploidy refers to a numerical change in a whole set of chromosomes. Organisms in which a particular chromosome, or chromosome segment, is under- or overrepresented are said to be aneuploid (from the Greek words meaning "not", "good", and "fold"). Therefore, the distinction between aneuploidy and polyploidy is that aneuploidy refers to a numerical change in part of the chromosome set, whereas polyploidy refers to a numerical change in the whole set of chromosomes.

Polyploidy may occur due to abnormal cell division, either during mitosis, or commonly during metaphase I in meiosis. In addition, it can be induced in plants and cell cultures by some chemicals: the best known is colchicine, which can result in chromosome doubling, though its use may have other less obvious consequences as well. Oryzalin will also double the existing chromosome content.

Polyploidy occurs in highly differentiated human tissues in the liver, heart muscle and bone marrow. It occurs in the somatic cells of some animals, such as goldfish, salmon, and salamanders, but is especially common among ferns and flowering plants (see "Hibiscus rosa-sinensis"), including both wild and cultivated species. Wheat, for example, after millennia of hybridization and modification by humans, has strains that are diploid (two sets of chromosomes), tetraploid (four sets of chromosomes) with the common name of durum or macaroni wheat, and hexaploid (six sets of chromosomes) with the common name of bread wheat. Many agriculturally important plants of the genus "Brassica" are also tetraploids.

Polyploidization is a mechanism of sympatric speciation because polyploids are usually unable to interbreed with their diploid ancestors. An example is the plant "Erythranthe peregrina". Sequencing confirmed that this species originated from "E. x robertsii", a sterile triploid hybrid between "E. guttata" and "E. lutea," both of which have been introduced and naturalised in the United Kingdom. New populations of "E. peregrina" arose on the Scottish mainland and the Orkney Islands via genome duplication from local populations of "E. x robertsii". Because of a rare genetic mutation, "E. peregrina" is not sterile.

Polyploid types are labeled according to the number of chromosome sets in the nucleus. The letter "x" is used to represent the number of chromosomes in a single set.

- triploid (three sets; 3"x"), for example seedless watermelons, common in the phylum Tardigrada

- tetraploid (four sets; 4"x"), for example Salmonidae fish, the cotton "Gossypium hirsutum "

- pentaploid (five sets; 5"x"), for example Kenai Birch ("Betula papyrifera" var. "kenaica")

- hexaploid (six sets; 6"x"), for example wheat, kiwifruit

- heptaploid or septaploid (seven sets; 7"x")

- octaploid or octoploid, (eight sets; 8"x"), for example "Acipenser" (genus of sturgeon fish), dahlias

- decaploid (ten sets; 10"x"), for example certain strawberries

- dodecaploid (twelve sets; 12"x"), for example the plants "Celosia argentea" and "Spartina anglica" or the amphibian "Xenopus ruwenzoriensis".

The hypothesis of vertebrate paleopolyploidy originated as early as the 1970s, proposed by the biologist Susumu Ohno. He reasoned that the vertebrate genome could not achieve its complexity without large scale whole-genome duplications. The "two rounds of genome duplication" hypothesis (2R hypothesis) came about, and gained in popularity, especially among developmental biologists.

Some researchers have questioned the 2R hypothesis because it predicts that vertebrate genomes should have a 4:1 gene ratio compared with invertebrate genomes, and this is not supported by findings from the 48 vertebrate genome projects available in mid-2011. For example, the human genome consists of ~21,000 protein coding genes according to June, 2011 counts at UCSC and Ensembl genome analysis centers while an average invertebrate genome size is about 15,000 genes. The amphioxus genome sequence provided support for the hypothesis of two rounds of whole genome duplication, followed by loss of duplicate copies of most genes. Additional arguments against 2R were based on the lack of the (AB)(CD) tree topology amongst four members of a gene family in vertebrates. However, if the two genome duplications occurred close together, we would not expect to find this topology. A recent study generated the sea lamprey genetic map, which yielded strong support for the hypothesis that a single whole-genome duplication occurred in the basal vertebrate lineage, preceded and followed by several evolutionarily independent segmental duplications that occurred over chordate evolution.