To review the origins of the Ophelia’s syndrome through the original description and its relation to Shakespeare’s character, and the related autoantibodies.

Ophelia’s syndrome is the association of Hodgkin’s Lymphoma and memory loss, coined by Dr. Carr in 1982, while it's most remembered for the eponym in reminiscence of Shakespeare’s character, Dr. Carr he prefigured neuronal autoantibodies at least 4 years before the first association with limbic encephalitis.

Narrative review, through literature search of Ophelia’s syndrome cases, its associated autoantibodies; and a comparison between Carr’s description and the Bard’s character.

In Hamlet, Shakespeare presents Ophelia, “divided from herself and her fair judgement”, from the grief that “springs all from her father’s death”. By rejecting Hamlet, she unkowingly sets in motion the events culminate in the death of Polonius by Hamlet’s sword; and eventually her own demise by in the “weeping brook”, while “incapable of her own distress”. As Carr predicted, “circulating neurotransmitter-like molecules” were eventually identified: anti-mGluR5; anti-Hu; anti-NMDAr; anti-SOX1 and anti-PCA2. Although in many other cases they have not been found. In almost all cases, tumour-directed therapy improves the neurologic syndrome. While reading Hamlet, we missed the association between Carr’s daughter and Ophelia: the former fights and defeats Hodgkin’s disease; the latter commits one of the most strange suicides in literature. Why did Dr. Carr associate them? “Is’t possible a young maid’s wits should be mortal as an old man’s life”; in the end, they decide to “take arms against a sea of troubles, and by opposing, end them”.

Dr. Carr’s description shares similarities with Hamlet’s ill-fated Ophelia: the inadvertent set in motion of events that culminate in self-inflicted harm (whether memory loss or suicide), that uncanningly correlates with pathophysiology of the syndrome.