Genoa ended Lazio's perfect start to the season thanks to a goal from former Roma striker Marco Borriello, despite an otherwise one-sided game at the Stadio Olimpico.
Lazio, who left Miroslav Klose on the bench, dominated most of the game but were restricted to long-distance efforts by a disciplined Genoa defence.
Borriello struck on the counter-attack in the 79th minute to condemn Lazio to their first defeat and lift the Rossoblu into the top half of the table.
Vladimir Petkovic decided to give Klose a rest in view of the upcoming midweek fixtures in Serie A, but by choosing Libor Kozak and Mauro Zarate in his attack, he lacked a cutting edge.
Indeed, the closest the Biancoceleste came to opening the scoring came from long-range shots from Hernanes and Antonio Candreva.
Genoa goalkeeper Sebastien Frey was equal to each and every one of them, thwarting Hernanes twice in the first 17 minutes and Candreva in the 28th.
Another Candreva shot was pushed behind for a corner by Frey, and Candreva's low cross shortly afterwards was just inches too far in front of Giuseppe Biava.
Hernanes got closer to scoring in the 47th minute with a shot against the top of the crossbar from just inside the penalty area.
Genoa slowly started to emerge from their shell and Borriello dragged a shot wide after a goalmouth scramble in the 60th minute.
At the other end, Kozak slid in and just missed the ball, again from Candreva's cross.
Klose was introduced in the 75th minute and, just a minute later, he came close to scoring with his first touch of the ball, cutting past Mario Sampirisi into the penalty area and placing his shot wide of the far post.
Genoa then struck on the break to take all three points thanks to Borriello.
The man who scored 19 goals for Genoa in his first spell with the club opened his account in his second spell by sending a low shot past Federico Marchetti after latching on to Luca Antonelli's clever through ball.