Jonah Lomu came through his first competitive match for almost three years as the Blues took maximum points.
HEINEKEN CUP POOL TWO
Calvisano (10) 10
Blues (13) 25
Tries: Sidoli, M. Williams, R. Williams, Czekaj
Con: N. Robinson
Pen: N. Robinson
The former All Black lasted an hour of his comeback from a kidney transplant, though he was kept quiet for most of the Heineken Cup Pool Two encounter.
Instead it was Robert Sidoli, Martyn Williams, Rhys Williams and Chris Czekaj who crossed for the Blues.
Apenisa Vodo scored a breakaway try for the home side, with Hercules Kruger converting and adding a penalty.
The Blues' win could have been much greater had Nick Robinson not missed four from six kicks.
All eyes were inevitably on Lomu as a sell-out crowd packed the tiny Centro Sportivo San Michele ground and they did not have to wait long for a glimpse of the big winger in action.
His first attacking burst led to the first try, as lock Sidoli strode over after seven minutes as the home side ran out of defenders.
Calvisano hit back five minutes later, though, when Fijian winger Vodo won the race for Van Schalkwyk's kick and Kruger converted to make it 7-8.
Wales flanker Williams profited from Michael Phillips' offload after 17 minutes following prolonged pressure, but further chances were squandered and their half-time lead was limited to 13-10 by a Kruger penalty.
The Blues finally broke clear on the hour mark with two tries while Calvisano prop Martin Castrogiovanni sat in the sin-bin.
Man-of-the-match Phillips created both, the first finished in the left corner by captain Williams, the second on the opposite side by Czekaj after Lomu had left the field to generous applause.
"It was always going to be tough but I'm just glad to have come through the 60 minutes without any injuries," said Lomu.
"It was only my first game back and I'm taking things steps by step. The most important thing is that we won the game.
"We're a team and that's what I'm part of so the most important thing is that the team does well not just me."
Calvisano: Van-Schalkwyk; Mulieri, Pratichetti, Zanoletti, A. Vodo; Kruger, Griffen; Perugini, Intoppa, M. Castrogiovanni, Ngauamo, Purll, Mandelli, Brosnihan, Zaffri.
Replacements: Cittadini, Ghiraldini, De Carli, Zanni, Patelli, Nitoglia, Ravazzolo.
Cardiff Blues: R. Williams; Czekaj, Stcherbina, Davies, Lomu; N. Robinson, Phillips; Yapp, R. Thomas, M. Jones, D. Jones, Sidoli, A. Powell, M. Williams, Rush.
Replacements: Jenkins, G. Williams, Quinnell, Sowden-Taylor, R. Powell, L. Thomas, J. Robinson.
Referee: Malcolm Changleng (Scotland)