Tomorrow night's clash is a repeat of last year's SWALEC Cup final where Keys claimed a memorable victory though it's Dale McIntosh's side who hold the bragging rights so far in this campaign.
The two sides met at Pandy Park on the opening weekend of the season, Ponty gaining revenge for their cup defeat with a convincing 3-28 win.
Encounters between the two sides are rarely for the faint hearted and both come into the game on the back of impressive wins last time out, Ponty away to Aberavon and Cross Keys at home to Llandovery.
Pontypridd once again make sweeping changes from the line up that secured that most recent victory, with McIntosh experimenting with a number of new combinations. Gareth Wyatt slots in at full back with Gavin Dacey and Gary Williams as a centre pairing.
Young props Chris Phillips and Bradley Thyer pack down alongside Kristian Dacey in the front row with Cory Hill returning from regional duties to partner skipper Chris Dicomidis at lock.
Absent for Ponty are winger Owen Jenkins, centre Tom Pascoe, outside half Simon Humberstone, scrum half Gareth James, prop Pat Palmer, hooker Jack Dando and second row Craig Locke.
Centre Adam Thomas and flanker Rhys Shellard are away with the Wales Sevens squad.
Cross Keys have struggled with consistency so far this season but seem to be hitting form in the run up to Christmas.
Their win over what were then league leaders Llandovery last week was promising and they will hope to avenge their defeat on the opening day of the season but know a trip to the House of Pain will be anything but easy.
They make five personnel changes and one positional change to the side that started in the victory over Llandovery last time out.
Keys once again include Steffan Jones, this time at full back with Jevon Groves coming in to the back row for the first time this season.
Pontypridd: 15 Gareth Wyatt 14 Lewis I Williams 13 Gavin Dacey 12 Gary Williams 11 Owen Williams 10 Dai Flanagan 9 Joel Raikes,
1 Chris Phillips 2 Kristian Dacey 3 Bradley Thyer 4 Cory Hill 5 Chris Dicomidis (c) 6 Jake Thomas 7 Wayne O'Connor 8 Owen Sheppeard.
Replacements: Carl Thomas, Geraint Walsh, Dafydd Lockyer, Darran Harris, Tom Hetherington, Ed Siggery, Keiron Jenkins, Scott Roberts.
Cross Keys: 15 Steffan Jones 14 Kristian Baller 13 Leon Andrews 12 Aled James 11 Elliot Jones 10 Dean Gunter 9 Rhys Dyer, 1 Richard Cornock 2 Gerwyn Price 3 Anthony Lott 4 Danny Hodge 5 Ollie Hodge 6 Jevon Groves 7 Rob Nash (c) 8 Adam Powell.
Replacements: Garry Horrigan, Craig Gould, Jamie Sollis, Scott Matthews, Ryan James, Dorian Jones, Gareth David.