Italy are desperate to end a dismal run of 14 successive defeats since making an unforgettable 6 Nations debut by beating Scotland three years ago.
And they might not have a better chance than against an injury-hit Welsh side at Rome's Stadio Flaminio.
The Italians, rejuvenated by New Zealander John Kirwan's arrival as their new coach, expect to produce some improved performances this season, and Wales could feel the heat first-up.
Wales though, have won all nine previous Tests against Italy, and will be in no mood to experience a miserable opening, just seven days before England arrive at the Millennium Stadium.
Injuries have deprived coach Steve Hansen of several experienced players - fly-half Stephen Jones, centre Jamie Robinson and hooker Robin McBryde are among the absentees.
But former rugby league star Iestyn Harris has a chance to show what he can do at No 10, while in-form Llanelli skipper Leigh Davies will provide midfield power.
In terms of selection, Kirwan has undoubtedly pulled the biggest surprise, switching outstanding Treviso flanker Mauro Bergamasco from the back-row to right-wing.
It is a bold move, but one which could pay off in spectacular fashion if Bergamasco is given enough possession to run at the Welsh defence.
Wales will look to take the game away from Italy early on, utilising a mobile back-row of Michael Owen, Martyn Williams and Colin Charvis, but Harris will also need to be on song with his goalkicking, otherwise it could be a long afternoon.
Italy have no such worries in that department, where veteran fly-half Diego Dominguez nerveless accuracy will undoubtedly punish any Welsh indiscipline.
It promises to be a nervy afternoon for both teams. Whichever team holds themselves together best, should prevail.
England flanker James Haskell insists he will be pushing as hard as possible to be back from a toe injury in time to make his case for a spot in Eddie Jones' side looking to defend their RBS 6 Nations title next year.