The first specifically anatomical investigation separate from a surgical or medical procedure is associated by early commentators with Alcmaeon of Croton. Leonardo da Vinci made notes for a planned anatomical treatise in which he intended to compare the hands of various animals including bears. Pierre Belon, a French naturalist born in 1517, conducted research and held discussions on dolphin embryos as well as the comparisons between the skeletons of birds to the skeletons of humans. His research led to modern comparative anatomy.
Around the same time, Andreas Vesalius was also making some strides of his own. A young anatomist of Flemish descent made famous by a penchant for amazing charts, he was systematically investigating and correcting the anatomical knowledge of the Greek physician Galen. He noticed that many of Galen's observations were not even based on actual humans. Instead, they were based on animals such as apes, monkeys, and oxen.  In fact, he entreated his students to do the following, in substitution for human skeletons, as cited by Edward Tyson : "“If you cant happen to fee any of thefe, diffect an Ape, carefully view each Bone, &c. …” Then he advifes what fort of Apes to make choice of, as moft refembling a Man : And conclude “One ought to know the Structure of all the Bones either in a Humane Body, or in an Apes ; ‘tis best in both ; and then to go to the Anatomy of the Mufcles.”" (Edward Tyson, Orang-Outang..., 1699, p. 59.) Up until that point, Galen and his teachings had been the authority on human anatomy. The irony is that Galen himself had emphasized the fact that one should make one's own observations instead of using those of another, but this advice was lost during the numerous translations of his work. As Vesalius began to uncover these mistakes, other physicians of the time began to trust their own observations more than those of Galen. An interesting observation made by some of these physicians was the presence of homologous structures in a wide variety of animals which included humans. These observations were later used by Darwin as he formed his theory of Natural Selection.
Edward Tyson is regarded as the founder of modern comparative anatomy. He is credited with determining that whales and dolphins are, in fact, mammals. Also, he concluded that chimpanzees are more similar to humans than to monkeys because of their arms. Marco Aurelio Severino also compared various animals, including birds, in his Zootomia democritaea, one of the first works of comparative anatomy. In the 18th and 19th century, great anatomists like George Cuvier, Richard Owen and Thomas Henry Huxley revolutionized our understanding of the basic build and systematics of vertebrates, laying the foundation for Charles Darwin's work on evolution. An example of a 20th-century comparative anatomist is Victor Negus, who worked on the structure and evolution of the larynx. Until the advent of genetic techniques like DNA sequencing, comparative anatomy together with embryology were the primary tools for understanding phylogeny, as exemplified by the work of Alfred Romer.
Two major concepts of comparative anatomy are:
- Homologous structures - structures (body parts/anatomy) which are similar in different species because the species have common descent and have evolved, usually divergently, from a shared ancestor. They may or may not perform the same function. An example is the forelimb structure shared by cats and whales.
- Analogous structures - structures similar in different organisms because, in convergent evolution, they evolved in a similar environment, rather than were inherited from a recent common ancestor. They usually serve the same or similar purposes. An example is the streamlined torpedo body shape of porpoises and sharks. So even though they evolved from different ancestors, porpoises and sharks developed analogous structures as a result of their evolution in the same aquatic environment. This is known as a homoplasy.
It also assists scientists in classifying organisms based on similar characteristics of their anatomical structures. A common example of comparative anatomy is the similar bone structures in forelimbs of cats, whales, bats, and humans. All of these appendages consist of the same basic parts; yet, they serve completely different functions. The skeletal parts which form a structure used for swimming, such as a fin, would not be ideal to form a wing, which is better-suited for flight. One explanation for the forelimbs' similar composition is descent with modification. Through random mutations and natural selection, each organism's anatomical structures gradually adapted to suit their respective habitats. The rules for development of special characteristics which differ significantly from general homology were listed by Karl Ernst von Baer as the laws now named after him.
- Gaucher EA, Kratzer JT, Randall RN (January 2010). "Deep phylogeny--how a tree can help characterize early life on Earth". Cold Spring Harbor Perspectives in Biology. 2 (1): a002238. doi:10.1101/cshperspect.a002238. PMC 2827910. PMID 20182607.
- "Science and Creationism". 1999-04-22. doi:10.17226/6024. Cite journal requires
- Blits KC (April 1999). "Aristotle: form, function, and comparative anatomy". The Anatomical Record. 257 (2): 58–63. doi:10.1002/(SICI)1097-0185(19990415)257:2<58::AID-AR6>3.0.CO;2-I. PMID 10321433.
- Bean, Jacob; Stampfle, Felice (1965). Drawings from New York Collections I: The Italian Renaissance. Greenwich, CT: Metropolitan Museum of Art. p. 28.
- Gudger EW (1934). "The Five Great Naturalists of the Sixteenth Century: Belon, Rondelet, Salviani, Gesner and Aldrovandi: A Chapter in the History of Ichthyology". Isis. 22 (1): 21–40. doi:10.1086/346870.
- Mesquita ET, Souza Júnior CV, Ferreira TR (March 2015). "Andreas Vesalius 500 years--A Renaissance that revolutionized cardiovascular knowledge". Revista Brasileira de Cirurgia Cardiovascular. 30 (2): 260–5. doi:10.5935/1678-9741.20150024. PMC 4462973. PMID 26107459.
- Caldwell R (2006). "Comparative Anatomy: Andreas Vesalius". University of California Museum of Paleontology. Archived from the original on 2010-11-23. Retrieved 2011-02-17.
- Kardong KV (2015). Vertebrates: Comparative Anatomy, Function, Evolution. New York: McGraw-Hill Education. pp. 15–16. ISBN 978-0-07-802302-6.
- Hardison RC (November 2003). "Comparative genomics". PLoS Biology. 1 (2): E58. doi:10.1371/journal.pbio.0000058. PMC 261895. PMID 14624258.
- Campbell NA, Reece JB (February 2002). Biology (6th ed.). San Francisco, CA: Benjamin Cummings. pp. 438–439. ISBN 978-0-8053-6624-2. OCLC 1053072597.
- Lőw P, Molnár K, Kriska G (2016). Atlas of Animal Anatomy and Histology. Springer. ISBN 978-3-319-25172-1.
- Wake MH, ed. (1979). Hyman's Comparative Vertebrate Anatomy (3rd ed.). University of Chicago Press. ISBN 978-0-226-87013-7.
- Zboray G, Kovács Z, Kriska G, Molnár K, Pálfia Z (2010). Atlas of comparative sectional anatomy of 6 invertebrates and 5 vertebrates. Wien: Springer. p. 295. ISBN 978-3-211-99763-5.