There are no early indications to suggest any kind of explosive device was on board the plane, although this will be a factor investigators will want to rule out.
The damage occurred in an area where baggage was being stored - indeed some bags are believed to have fallen through the hole.
But that does not necessarily indicate that a bag was the source of the problem.
Anything large enough to have caused this level of damage - either accidentally or deliberately - should theoretically have been picked up by airport security checks.
Airline security levels and procedures have changed dramatically since a bomb was placed in luggage on board Pan Am Flight 103 from London Heathrow to New York's JFK on December 21 1988 - blowing it up in midair above Lockerbie. In that incident - involving a Boeing 747-121 - 270 people died on the plane and on the ground .
However, the possibility of a problem within passengers' luggage is certainly an area investigators will want to rule out.
Corrosion focus?
Other attention has focused on oxygen cylinders - or possibly even fire extinguishers - which are also carried in that part of the plane.
No indication has emerged of circumstances which would have caused one of the cylinders to explode, but again this is likely to be an area of focus for the investigators.
The maintenance of the plane will also be under close scrutiny, and could well be where the inquiry has its main focus.
The plane - registration VH-OJK - is believed to have been delivered to Qantas in 1991, so the airline's maintenance of it throughout those 17 years should be available to investigators if required.
Officials may want to seek confirmation that normal checks have been carried out properly, and that any previously known problems were dealt with satisfactorily.
In particular, officials are likely to want to check for possible corrosion in the area where the damage occurred.
Corrosion could plausibly have been enough to have caused the damage - if even a small section of the plane's aluminium skin was able to break free, the enormous pressures generated at cruising altitude could have been enough to do the rest.
Other possible causes might include accidental external damage to the plane on the ground, or something inside the plane which had not been properly secured and slammed into the fuselage at some point.
Worst-case scenarios
And remaining at the forefront of many minds - not least of those on board - will be a "what might have been" scenario.
If debris from the hole had been sucked into the engines, could the pilots have been dealing with engine failure or loss as well as an emergency descent?
Or if the structural damage had passed a certain "tipping point", could the plane have started to break up in mid-air?
Certainly part of the flooring near the affected section is said to have given way, exposing some of the cargo below, and part of the ceiling also collapsed - although this may have been part of the plane's built-in "responses", giving way in a planned manner to prevent even greater pressures building up on the main structure.
As it was, the mid-air drama ended with more than 360 people walking off the plane suffering from nothing worse than severe shock and vomiting. They and the investigators will be thankful the investigation is focusing on a hole in a fuselage, not the loss of a Boeing over the South China Sea.
