Equivalent puckered conformations interconvert: Despite the inherent strain, the cyclobutane motif is indeed found in nature.

The compound is found in bacteria performing the anammox process where it forms part of a tight and very dense membrane believed to protect the organism from toxic hydroxylamine and hydrazine involved in the production of nitrogen and water from nitrite ions and ammonia.

[citation needed] Cyclobutane photo dimers (CPD) are formed by photochemical reactions that result in the coupling of the C=C double bonds of pyrimidines.

Xeroderma pigmentosum is a genetic disease where this damage can not be repaired, resulting in skin discolouration and tumours induced by exposure to UV light.

Cyclobutane was first synthesized in 1907 by James Bruce and Richard Willstätter by hydrogenating cyclobutene in the presence of nickel.