It is the second time Halfpenny has found himself in a race against time to play in rugby's biggest events.
In 2009, he strained a thigh muscle just two weeks ahead of the Lions tour. He was sent home from South Africa for further treatment and returned to appear in the third game of the tour, against the Cheetahs, only to break down again.
Halfpenny was expected to play some part in Wales' World Cup warm-up fixtures but has now been told he could be sidelined for as long as four months.
That will exclude the youngest member of the 2009 Lions party from taking any part in the games against the Barbarians, England (twice) and Argentina before Wales coach Warren Gatland names his 30-man World Cup squad on August 22.
And with just three weeks between the squad announcement and the opening tournament clash with South Africa on September 11, Halfpenny's place in the squad seems to be in real doubt.
"Leigh has an ankle problem that still needs looking at," said Gatland, who refused to speculate too heavily on Halfpenny's World Cup chances.
"Right now he is out for as long as 16 weeks, which takes him right to the cusp of the World Cup. We will have to see how things go."
Halfpenny has endured a torrid season as far as injuries are concerned.
The 22-year-old former Wales Youth star missed the start of the Six Nations, as well as the entire autumn series, with the same complaint.
He appeared to be edging back to his best in the latter part of the season but then hobbled out of the Blues' victory over Treviso on April 21.
Halfpenny spent time on crutches and was initially ruled out for six weeks but that diagnosis was well short of the mark.