Isomerism was first observed in 1827, when Friedrich Wöhler prepared silver cyanate and discovered that, although its elemental composition of  was identical to silver fulminate (prepared by Justus von Liebig the previous year), its properties were distinct. This finding challenged the prevailing chemical understanding of the time, which held that chemical compounds could be distinct only when their elemental compositions differ. (We now know that the bonding structures of fulminate and cyanate can be approximately described as ≡ and , respectively.)
Additional examples were found in succeeding years, such as Wöhlers 1828 discovery that urea has the same atomic composition () as the chemically distinct ammonium cyanate. (Their structures are now known to be  and , respectively.) In 1830 Jöns Jacob Berzelius introduced the term isomerism' to describe the phenomenon.
In 1848, Louis Pasteur observed that tartaric acid crystals came into two kinds of shapes that were mirror images of each other. Separating the crystals by hand, he obtained two version of tartaric acid, each of which would crystallize in only one of the two shapes, and rotated the plane of polarized light to the same degree but in opposite directions. In 1860, Pasteur explicitly hypothesized that the molecules of isomers might have the same composition but different arrangements of their atoms.