Aylmer, an accomplished scientist, has taken a break from his laboratory to marry a beautiful woman named Georgiana, although it’s suggested that his love for her can probably never quite match his devotion to science. After their wedding, Aylmer becomes fixated on the small, hand-shaped birthmark on his wife’s left cheek, the only physical imperfection of an otherwise perfect woman. Georgiana’s former suitors have never minded the birthmark, and so she herself has not thought much of it. But now, Aylmer’s revulsion at the birthmark disturbs all of the couple’s happy times together, and Georgiana begins to dread his gaze on her cheek.
One evening, Georgiana recalls to Aylmer that the night before, he had a dream that he tried to cut the birthmark out of her cheek, but it receded into her heart until he would have to cut it out of that vital organ. Distressed at her husband’s hatred of her appearance, Georgiana suggests that he should, in fact, make an attempt to remove the birthmark. Aylmer agrees, eager to join his love of science to his love of Georgiana and to test his scientific abilities.
The next day, Aylmer brings Georgiana to his laboratory, where she immediately faints. Aylmer’s assistant, Aminadab, emerges. He is a rough, strong man who does the physical work of the lab. He remarks that if it were up to him, he wouldn’t remove the birthmark. Georgiana wakes and is dazzled by the ethereal beauty of the room that Aylmer has prepared for her. He demonstrates gorgeous scientific wonders for her, but some of them fail and only make their subjects ugly. He then boasts of great scientific feats, such as creating life and making an elixir that would make the drinker immortal, that he could accomplish if only he thought it moral to try, which he doesn’t.
Finally, Georgiana looks through a number of books in Aylmer’s library that detail the work of famous earlier scientists, as well as Aylmer’s own experiments. She realizes that her husband has fallen short of many of the discoveries he hoped to accomplish. However, this only makes her admire him even more for aiming at such lofty goals. She enters the inner room of the laboratory and sees Aylmer and Aminadab working anxiously. She realizes that Aylmer is more worried about the treatment than he’s let her see. He gets angry when he sees her in the lab, thinking that she doesn’t trust him. She tells him that, to the contrary, she’ll go through with the experiment no matter what, so he should tell her how dangerous it really is. He admits that he has already been subjecting her to treatments without her knowledge, and they haven’t worked.
Back in the outer room, Aylmer pours a liquid onto a diseased plant, which immediately becomes healthy again. He then has Georgiana drink the liquid. She falls asleep, and Aylmer keeps watch over her, at one point kissing the birthmark. Soon the mark begins to disappear, and Aylmer is overjoyed. Georgiana wakes and, pitying Aylmer, tells him that she is dying. While Aminadab laughs, Georgiana dies, for with the disappearance of her only flaw and mark of mortality, she has become too perfect to remain on the earthly plane.