The pinnacle of Signori's career came at Lazio, where he was the top goalscorer in Serie A three times, in 1993, 1994, and 1996 (the last title shared with Igor Protti). In 1998, he was sold for an undisclosed figure to Sampdoria after being used more sparingly by the Lazio coach Sven-Göran Eriksson. At Bologna, he helped the club to qualify for the 1998–99 UEFA Cup by winning the 1998 UEFA Intertoto Cup that season. Bologna went on to reach the semi-finals of both the UEFA Cup and the Coppa Italia that season. Overall, he scored 188 goals in Italy's top division, the ninth highest in the history of the league, alongside Alessandro Del Piero and Alberto Gilardino.