Antonio Candreva and Keita Balde were on target against their former club as Inter's eight-match winning run in Serie A ground to a halt in a 2-1 defeat at Sampdoria.
The Nerazzurri were aiming to go top, at least temporarily, and Alexis Sanchez saw an early penalty saved at the Luigi Ferraris.
Another VAR check led to Candreva opening the scoring from the spot and Keita – on loan at Sampdoria from Monaco – doubled the hosts' lead in an enthralling first half.
Stefan de Vrij finally headed wasteful Inter onto the scoreboard after 65 minutes, but Antonio Conte's side failed to find a leveller and remain second, one point adrift of Milan.
In a breathless opening, Emil Audero foiled Ashley Young's whipped shot and Milan Skriniar skewed wide from the same corner that saw Morten Thorsby pinged for handball after the VAR's intervention.
Audero kept out Sanchez's penalty and Young smashed the rebound against the post, while Lorenzo Tonelli's looping header for Sampdoria hit the crossbar soon after.
Candreva succeeded where Sanchez failed after 23 minutes, firing into the left of the goal after VAR spotted Nicolo Barella had handled a Tonelli header.
Things worsened for Inter when Keita swept home Mikkel Damsgaard's low right-wing centre seven minutes before the break.
Sanchez was denied by Audero again and Lautaro Martinez wastefully headed wide, before the former followed suit in similar style after the break.
Inter finally responded when de Vrij headed home Marcelo Brozovic's corner with 25 minutes left and substitute Romelu Lukaku saw a powerful downward header brilliantly stopped by Audero.
Ivan Perisic was twice off target with headers either side of Martinez testing Audero at his near post but Inter were frustrated in their endeavours.