Quagliarella had a fourth-minute goal chalked off for offside following a VAR review and the technology was also used to confirm Empoli a penalty converted by Manuel Pasqual in the 11th minute.
After Gaston Ramirez equalised in the 41st minute, Samp were awarded a penalty early in the second half for a foul by Matias Silvestre on Lorenzo Tonelli but the referee reversed his decision nearly three minutes later after another review.
Quagliarella, 35, put Sampdoria in front, continuing his remarkable run, before Francesco Caputo equalised for Empoli amid more confusion as his goal was first disallowed for offside, then allowed to stand following a VAR review.
Two late goals from Gianluca Caprari settled the game for Samp, who climbed to sixth, and there was still time for another VAR episode as Antonino La Gumina had a third Empoli goal chalked off for offside.
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There was more VAR drama at Sassuolo where Torino had a stoppage-time winner disallowed.
Andrea Belotti put Torino ahead in the 54th minute, Enrico Brignola headed the equaliser in the second minute of stoppage time before Iago Falque had the ball in the net for the visitors, only to see it ruled out for offside after a long review.
Genoa striker Krzysztof Piatek, Serie A's leading score, hit his 14th goal of the season to complete a 3-1 win over Atalanta which gave their former Italy coach Cesare Prandelli his first win since taking over.
Genoa's first win for nearly three months lifted them to 13th with 19 points.
(Reporting by Brian Homewood, editing by Ed Osmond)
