The two unbeaten sides in Pool 4 go head-to-head at Rodney Parade on Thursday with Newport Gwent Dragons hosting Perpignan.
The likely talking point ahead of the game will focus around the return of James Hook to Wales. The fly-half scored all of Perpignan's points last weekend as they came back to beat Exeter Chiefs at home. Hook, who is in his first season in French rugby will line-up against a host of Welsh colleagues at Newport.
The Dragons have only ever appeared in the Amlin Challenge Cup once, back in 2006 when they made the semi-finals and Darren Edwards's men will be targeting a knock-out stage place this time around.
Perpignan reached the last four of the Heineken Cup last season but have had mixed fortunes in the TOP14 so far this campaign.
Exeter Chiefs v I Cavalieri Prato
(Saturday November 19, KO 15.00)
Exeter came within a whisker of beating Perpignan in the south of France last weekend but had to settle for a losing bonus point and so will be keen to record their first victory of their 2011/12 campaign when they welcome I Cavalieri Prato to Sandy Park.
The Chiefs impressed last term in their debut European season but will be looking to go one better this time around and reach the knock-out stages.
I Cavalieri Prato struggled in their opening game this season, losing 3 v 33 at home to the Dragons.
The record books show only one victory in their European history so it will be a tough task for the Italian side on their visit to the south west of England.