The duo were nicknamed 'Moliwood' following their heroics against the United States in Paris in 2018, when they won four points from four together.
And they were back together again at Marco Simone Golf & Country Club, playing in the same group on Thursday and Friday.
Fleetwood made a strong start to the tournament, following up an opening 66 which he shot in tricky conditions on Thursday with a second round 68 to get to eight under par.
Things could have been even better for the Englishman had he not carded a double bogey at the 17th hole of his round on both days.
But he heads into the weekend in a healthy position as he goes in search of a sixth European Tour title.
It’s impossible to not enjoy playing golf in Italy with this man!!! pic.twitter.com/xhMl6IoahJ— Tommy Fleetwood (@TommyFleetwood1) September 3, 2021
Speaking about playing with home favourite Molinari, Fleetwood said: "It’s always nice.
"It doesn’t make that much of a difference but at the same time, it is nice to play with someone you are very comfortable with and it’s always nice to see each other - and then we have ten hours together over the first two days to talk and play.
"Like I say, there is probably not another golfer out here that I feel as comfortable with playing so that does add to the ease of playing tournament golf."