Leicester claimed a gutsy first-leg win away at three-time runners-up Clermont Auvergne to take a stride towards the Champions Cup last eight.
After an early Clermont try, Ellis Genge and Julian Montoya ground their way over to make it 10-10 at half-time.
Jack van Poortvliet and Hosea Saumaki crossed as the Tigers turned the screw, moving 12 points clear after the break.
Guy Porter's red card did not derail Leicester, with Harry Potter added a fifth try as Clermont lost discipline.
Leicester's dominance despite depleted numbers, combined with their form - this was their 25th win in 29 matches in all competitions this season - makes them hot favourites to meet either Leinster or Connacht in the last eight.
The teams meet again at Welford Road next Saturday with aggregate scores over the two matches deciding which progresses.
Tigers show fighting spirit to overcome red
The physicality of the fixture was underlined in the opening minutes as Clermont flanker Judicael Cancoriet floored full-back Freddie Steward with a shuddering hit.
The hosts showed the beauty that comes with their brute strength with a superb opening score, the ball zipping out to the left wing where Cheikh Tiberghien stepped inside the cover to dive over.
Leicester have plenty of grit and gristle to the their game this season though. The Tigers are well clear at the top of the Premiership and have been reborn under the guidance of head coach Steve Borthwick.
Captain Genge thundered over the top of hooker Etienne Fourcade from close range to get the visitors on the board, before front-row colleague Montoya followed suit at the back of a collapsed maul.
Morgan Parra's accuracy with the boot ensured the sides headed into the break level on the scoreboard.
However, 20-year-old Van Poortvliet got one up on Parra, 13 years his senior, for the first try of the second half.
The Tigers scrum-half spotted an understaffed blind-side as the hosts braced themselves for another driven maul off a line-out five metres out before darting, dummying and diving in for a fine score.
Clermont's threat was never extinguished with the powerful Alivereti Raka bristling with danger every time he got his hands on the ball.
But the visitors were the more clinical with their openings. George Ford and Steward spun wide with speed and accuracy to feed Saumaki for a fourth score.
Ford's conversion, his first successful shot at goal of the afternoon, gave the visitors a 22-10 lead and further dampened the fervour of the Stade Marcel Michelin.
The home crowd were not quiet long. When Porter clashed heads with number eight Fitz Lee - an apparently accidental collision on both parts - they howled for a red card. The referee obliged and it seemed Leicester would have to hang on for victory.
Instead the 14-man Tigers romped home.
Steward set up Potter's 65th-minute score with a superb overhead take of a Ford up-and-under and it could have been more with Leicester camped in Clermont territory late on and Montoya denied a second score by the television match official.
Line-ups
Clermont-Auvergne: Matsushima; Raka, Moala, Fofana, Tiberghien; Lopez, Parra; Beria, Fourcade, Slimani, Jedrasiak, Vahaamahina, Cancoriet, Fischer, Lee.
Replacements: Beheregaray, Falgoux, Ojovan, Amatosero, Dessaigne, Viallard, Hanrahan, O'Connor
Leicester: Steward; Potter, Porter, Kelly, Saumaki; Ford, Van Poortvliet; Genge (capt), Montoya, Heyes, Chessum, Green, Liebenberg, Reffell, Wiese
Replacements: Dolly, Whitcombe, Cole, Wells, Snyman, Wigglesworth, Burns, Moroni