Sampdoria dominated Napoli and ruined their perfect record with a 3-0 drubbing at the Stadio Luigi Ferraris on Sunday.
Things were going well for Sampdoria as a first-half brace from Grégoire Defrel had the hosts up 2-0 against Carlo Ancelotti's men.
Although Napoli improved after the break, Quagliarella backheel flick put an end to their challenge.
Off a free-kick that was sent off the wall, defender Bartosz Bereszyński decided to drive a hard low cross into the area.
Quagliarella, with his back toward goal, managed not only to get to the cross but also turn it into a magical finish.
The 35-year-old striker reached back his right heel to flick it upwards and behind him to dip into the far bottom corner from nine yards.
Quagliarella has a knack for scoring fine goals over the years, but this one has to be the very best of his career.
Speaking to Sky Sport Italia, the former Italy international said:
When I saw the cross coming in, I had a fraction of a second to decide.
I thought if I go with the inside of the boot, I'm never getting that on target, so I had to go for the heel and hope for the best. It went well in the end.
Is it my best ever goal? No… it's in the top three, but I scored from midfield a couple of times, so there are others to choose from.