Not since Coimbra's involvement in 2005 has Portugal welcomed top level club rugby and Lusitanos will aim to match the occasion against the powerful English outfit.
London Irish matched Stade Francais' result the previous night in the opening round by beating Cavalieri 60-11 at the Madejski Stadium.
Sailosi Tagicakibau clinched a bonus point before half-time before Fergus Mulchrone crossed twice in the nine-try success.
Now they will venture to new territory in Portugal as they aim to progress to the quarter-finals for the first time in six years.
Stade Francais went all the way to the final last season and sent a clear statement of intent on the opening weekend.
In Jerome Porical they have one of the tournament's finest points scorers. Adept with the boot, after converting six of his team's nine tries, the Perpignan-born full-back also weighed in with two tries of his own as Stade brushed past Lusitanos 61-3 in Paris.
I Cavalieri Prato will also have to find a way to stop veteran wing Julien Arias, who extended his remarkable scoring run to 29 tries in all European competitions with a double against the Portuguese.