The Stoop has been chosen to stage the Amlin Challenge Cup final for the fourth time.
It will take place on Friday 18 May at 2000 BST, just hours before the Heineken Cup final at Twickenham.
Derek McGrath, chief executive of organisers ERC, promised "two compelling rugby occasions".
He said: "Following on from the success of last season, when both finals were staged in Cardiff, this will be another celebration of European club rugby."
Harlequins, who play their home games at The Stoop, won a thrilling 2011 final in May when a late converted try by Gonzalo Camacho earned them a 19-18 victory over Stade Francais.
It also earned them a place in this season's Heineken Cup and they will face Toulouse at The Stoop on Friday in their latest group game.