Cytosine was discovered and named by Albrecht Kossel and Albert Neumann in 1894 when it was hydrolyzed from calf thymus tissues.

In 1998, cytosine was used in an early demonstration of quantum information processing when Oxford University researchers implemented the Deutsch–Jozsa algorithm on a two qubit nuclear magnetic resonance quantum computer (NMRQC).

The difference in rates of deamination of cytosine and 5-methylcytosine (to uracil and thymine) forms the basis of bisulfite sequencing.

[8] When found third in a codon of RNA, cytosine is synonymous with uracil, as they are interchangeable as the third base.

Until October 2021, Cytosine had not been found in meteorites, which suggested the first strands of RNA and DNA had to look elsewhere to obtain this building block.