Ulster host Benetton Treviso on Friday night at the Kingspan Stadium - the venue for this year's GUINNESS PRO12 final - as league action returns from a month-long break.
And the clash presents fly-half Humphreys with the opportunity to join the competition's 500 club - he will need nine points on the night to reach the milestone.
The 32-year-old could also close in on his most prolific adversaries, with Ospreys' Dan Biggar, Leinster's Ian Madigan and Munster man Ian Keatley each occupied by international duty.
Those three have each racked up a century already this season and Humphreys - currently fourth in the points table with 81 - could well close the gap on Friday.
Another man who may well capitalise from Keatley's international duties is Munster fly-half JJ Hanrahan.
The Irish province host Cardiff Blues on Saturday and it is a happy fixture for Hanrahan after the 22-year-old slotted a competition-high seven penalties at Thomond Park last season.
Meanwhile, on the other side, Welsh international flanker Josh Turnbull will make his 100th GUINNESS PRO12 appearance if he features in Limerick.
Up in Scotland, Edinburgh will host Ospreys at BT Murrayfield and fans of both sides may well be expecting a high-scoring contest.
The reverse fixture was both the highest-scoring game in the GUINNESS PRO12 last season and the biggest margin of victory, as the Ospreys ran out 62-13 winners at the Liberty Stadium.
Elsewhere, Connacht travel to Parc y Scarlets, where Wayne Pivac's side have not lost their last dozen PRO12 fixtures.
Zebre will play their first in the re-named Stadio Lafranchi as they seek a first ever victory against high-flying Glasgow Warriors.
And the next challengers to end Leinster's unbeaten record in 2015 are Newport Gwent Dragons, the Welsh region visitors to the RDS on Sunday.
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