Sassuolo were the victims of a giant-killing defeat to Perugia in the Coppa Italia fourth round, while Bologna were thrashed by Serie A rivals Udinese.
Perugia are in the mix for an automatic promotion place in Serie B, and they took that momentum to Mapei Stadium, stunning the hosts 2-1.
Pasquale Mazzocchi and Juventus loanee Hans Nicolussi scored inside 17 minutes for Massimo Oddo’s side, who then faced a Sassuolo onslaught.
Despite their dominance thereafter, the Neroverdi could only respond with a Mehdi Bourabia consolation in the 82nd minute.
SPAL, on the other hand, had no such problems, comfortably dispatching relegation rivals Lecce 5-1.
Leonardo Semplici will have been delighted to see five different players get on the scoresheet for the hosts in Igor, Alberto Paloschi, Alessandro Murgia, Thiago Cionek and veteran Sergio Floccari.
Lecce, who were never truly at the races, did pull one back through Giannelli Imbula just before the hour mark.
Finally, Udinese scored twice either side of half-time to rout Bologna 4-0.
Antonin Barak and ex-Rossoblu defender Sebastien De Maio put the Zebrette ahead, before Rolando Mandragora and Kevin Lasagna at the death rounded off the result.
Perugia face Napoli in the last 16, SPAL get Milan and Udinese are drawn Juventus, with the ties to be played mid-January.
Watch Serie A live in the UK on Premier Sports for just £11.99 per month including live LaLiga, Eredivisie, Scottish Cup Football and more. Visit:https://subscribe.premiersports.tv/