Titans Director of Rugby Steph Nel believes the Round 1 first leg clash at Sergio Lanfranchi provides the Yorkshire club with the opportunity to kick-start their campaign with that all important first victory.
"In the two months I have been at Rotherham there has been a huge improvement - quite massive," said Nel.
"The work rate of the players has been superb and the next step is to get a win. From that other benefits will flow."
But it will be something of a step into the unknown for the Titans, Nel admitting "we know very little about them but expect them to be largely similar to all Italian sides.
"That means we will have to stay fully disciplined and try and sneak a win by playing good rugby and being solid in defence. If we can do that we should be okay and then be able to look forward to the second leg at our ground."
Rotherham, knocked out of the Parker Pen Challenge Cup by Narbonne, went agonisingly close to breaking their season's duck against Zurich Premiership leaders Bath Rugby last weekend."We had them," said Nel. "But in the final few minutes of injury time we conceded a couple of tries. It was very disappointing but we will keep hammering away for that elusive first win."
Scrum-half Jacob Rauluni returns to captain the side after missing the weekend encounter with Bath.
Joe Ewens and Michael Wood return on the wings as all of the recent signings are not registered for European competition.
Leon Greeff returns after an outstanding 'A' team performance with crowd favourite Simon Bunting taking his place on the bench.
Rotherham: 15 Bernardo Stortoni 14 Joe Ewens 13 Jon Pritchard 12 Mike Umaga 11 Michael Wood 10 Jon Benson 9 Jacob Rauluni (capt.) 1 Nick Lloyd 2 Chris Johnson 3 John Rawson 4 Glen Kenworthy 5 Jonathon Pendlebury 6 Leon Greeff 7 Craig Short 8 Geraint Lewis
Replacements: 16 Simon Bunting 17 Colin Noon 18 Luke Gross 19 Charlie Harison 20 Matthew Rhodes 21 Phil Jones 22 Peter Jorgensen