Goalkeeper Pau Lopez was the second Roma player to be shown a red card at the start of extra time against Spezia
Roma were knocked out of the Coppa Italia by Spezia after a chaotic extra-time period that included one more substitution than they were allowed and two red cards.
The hosts had fought back from 2-0 down to force the extra half an hour in the last-16 tie - but they were reduced to nine men within two minutes of the restart as their evening unravelled.
First, Gianluca Mancini was sent off after picking up a second booking, then the Giallorossi had goalkeeper Pau Lopez dismissed after he made a mess of a clearance and took out a Spezia forward in the process.
Boss Paulo Fonseca quickly made a double change - Roger Ibanez replacing Pedro and midfielder Bryan Cristante being sacrificed to allow keeper Daniel Fuzato to come on.
Problem was, that took Roma's substitutions up to six when only five are permitted.
In the end, the error mattered little. Roma only held on until the 107th minute before Daniele Verde made it 3-2, and then Riccardo Saponara added a fourth for Spezia four minutes later.
When asked about the extra substitute, Fonseca said: "If there is an issue, we have time to discuss that internally."
The Portuguese said it became "much harder" after the two red cards and that the Serie A side, who were beaten 3-0 by city rivals Lazio five days earlier, are in "a tough moment".
Earlier this season, Roma were penalised with a 3-0 defeat following an administrative error in the make-up of their matchday is squad for September's 0-0 league draw against Hellas Verona.
- Line-upsMatch Stats
13López23Mancini4Cristante24Kumbulla33da Silva Peres7Pellegrini14Villar37Spinazzola11Pedro77Mkhitaryan21Mayoral
- 13LópezBooked at 92mins23ManciniBooked at 91mins4CristanteSubstituted forCerantola Fuzatoat 95'minutes24Kumbulla33da Silva Peres7PellegriniBooked at 111mins14VillarSubstituted forVeretoutat 69'minutes37SpinazzolaSubstituted forKarsdorpat 69'minutes11PedroSubstituted forIbañez da Silvaat 95'minutes77MkhitaryanSubstituted forPérezat 85'minutes21MayoralSubstituted forDzekoat 90'minutes
- 2Karsdorp3Ibañez da Silva5Nunes Jesus6Smalling9Dzeko12Farelli17Veretout18Santon20Fazio31Pérez64Podgoreanu87Cerantola Fuzato
12Krapikas69Vignali34Ismajli28Erlic3Ramos27Deiola88de Souza Sena25Maggiore80Agudelo9Galabinov23Saponara
- 12Krapikas69Vignali34IsmajliBooked at 24mins28Erlic3RamosSubstituted forDell'Orcoat 68'minutesBooked at 90mins27DeiolaSubstituted forAcamporaat 80'minutes88de Souza SenaSubstituted forRicciat 68'minutes25Maggiore80AgudeloBooked at 13minsSubstituted forVerdeat 59'minutes9GalabinovSubstituted forPiccoliat 68'minutes23Saponara
- 1Zoet4Acampora8Ricci10Agoume11Gyasi17Farias19Terzi22Chabot31Verde39Dell'Orco77Bittencourt Pinheiro91Piccoli
Referee:Davide GhersiniMatch StatsHome TeamRomaAway TeamSpeziaPossessionHome50%Away50%ShotsHome17Away13Shots on TargetHome4Away8CornersHome7Away4FoulsHome18Away23
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