Shock results have speckled the sport's landscape since, not least Lennox Lewis' one-punch dethroning by Hasim Rahman in South Africa in April 2001, albeit subsequently and swiftly avenged.
But placed in the context of both the colossal expectations and the nature of its execution, Anthony Joshua's defeat to late substitute Andy Ruiz Jr in New York on Saturday night shook up the division like few other bouts before it.
For one, it shatters the prospective narrative of rivalries and trilogies between Joshua, Tyson Fury and Deontay Wilder which was - politics permitting - to have lit up the heavyweight division for the best part of a decade to come.
Fury and Wilder, who are reportedly close to agreeing to a rematch early next year, suddenly find themselves united again on centre-stage, while Joshua faces up to an enormous task of rehabilitation.
One-punch knockouts are one thing. Four-knockdown, aura-shattering exits are something completely different.
The man who was to be boxing's first billionaire athlete suddenly finds himself facing the prospect of scrabbling for his sport's loose change.
Here, Press Association Sport considers the changed prospects of arguably the five biggest names in the heavyweight division, and takes a stab at what might be in store:
Deontay Wilder
Wilder might have splattered all before him Stateside but it was not until his split decision draw against Fury last December that he truly emerged as his division's likely leading light. Wilder would arguably be favoured to overcome the Briton in a rematch - reportedly close to being signed for January next year - which would elevate him to the position of undisputed number one.
Tyson Fury
In light of his comeback from a long period of inactivity, Fury's performance against Wilder was extraordinary. A more serious and sustained build-up would raise his chances of winning a rematch, but either way, Fury now finds himself in a position of considerable power, as the only realistic pretender to the crown that Wilder, as the WBC belt-holder, currently wears.
Anthony Joshua
Forget stadium-filling superstardom: Joshua faces a gruelling road back to the top. Even a win over Ruiz in an immediate rematch - which is surely his only option - would not assuage the doubts. For the time being he must forget about his division's big two, and set about learning the kind of crafts his PR-spun sweep to the disputed pinnacle of his sport left him so dismally unprepared for.
Andy Ruiz Jr
Whatever happens next, Ruiz Jr has set himself up for life. Besides its financial rewards, a rematch will either propel him towards super-fights with the likes of Wilder and Fury, or else see him relegated to the still-lucrative role of staging-post for a future generation of contenders. Ruiz Jr may not be chiselled like a champion, but his record - and his performance against Joshua - illustrate that he is certainly not one to be taken lightly.
Dillian Whyte
Whyte's chances of a rematch with Joshua - whom he wobbled in 2015, and probably spent much of Saturday night wondering what might have been - have arguably improved. If Joshua wins a rematch with Ruiz, Whyte would be an ideal first challenger. And unlike the first meeting, for which Joshua was the heavy favourite, the pair would enter the ring with many more questions raging about the bout's potential outcome.
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