Napoli ran riot in Rome on Sunday with a 4-1 victory which pushed Roma out of the European places and consolidated second place for Carlo Ancelotti's side in Serie A ahead of Inter Milan who fell 1-0 at home against Lazio.
Juventus closed in on an eighth consecutive Serie A title with on-form teenager Moise Kean scoring the only goal against Empoli on Saturday.
Napoli -- a massive 15 points behind -- have almost no chance of winning the title for the first time since 1990 with nine games to go, but have now a ten-point cushion on third-placed Inter.
Lazio, with a game in hand, moved up to fifth, three points behind AC Milan who occupy the final Champions League berth and also fell 1-0 to Sampdoria. Sergej Milinkovic-Savic sealed the three points for Lazio after 13 minutes in the San Siro.
"It's a heavy defeat against a direct rival," said Inter coach Luciano Spalletti.
"We controlled the game for long periods, but were unlucky to waste our chances and then go behind, allowing Lazio to dictate their style of play."
In Rome, Arkadiusz Milik put the visitors ahead after two minutes with Dries Mertens, Simone Verdi and Amin Younes adding three more in the second half to inflict another blow on the hosts' Champions League ambitions next season.
"I expected a performance like this, the team is growing," said Carlo Ancelotti, whose side are building towards a Europa League quarter-final clash against Arsenal.
"We were masters of the pitch."
It was a further blow for Roma coach Claudio Ranieri in just his third game since taking over from Eusebio Di Francesco as the Romans fell to their second consecutive defeat after lowly SPAL last time out.
"It's tough. We're going through a period where we concede from the first attack," said former Leicester boss Ranieri.
"Do I regret having accepted Roma? Never. I could never regret training this club," he added.
"We're doing everything we can, but we're not giving up."
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Roma are in danger of missing out on European football altogether as they drop to seventh, a point outside the Europa League places.
Atalanta are in sixth after a 3-1 comeback win against Parma.
Ancelotti's Napoli dominated against the club where he spent eight seasons as a player.
Roma were struggling to keep up from the start when Verdi sent the ball over for Milik to blast the visitors ahead early.
The Polish striker had a second goal disallowed for offside before Diego Perotti pulled Roma level just before the break with a penalty after a foul on Patrik Schick.
But hopes of a revival were short-lived with Mertens tapping in a second four minutes after the break off a Jose Callejon assist.
Verdi piled more pressure on Ranieri's side with a third on 54 minutes following good work by Fabian Ruiz on the counter attack.
Roma had chances with Napoli goalkeeper Alex Meret denying Bryan Cristante with Steven Nzonzi heading the rebound onto the bar.
But Younes compounded the misery of the hosts, adding the fourth nine minutes from time following a scramble on front of goal after a poorly cleared corner.
"It's a bit of everything -- the physical level, the mental level and the injuries," added Ranieri.
Colombian striker Duvan Zapata scored a late brace in a 3-1 comeback win for Atalanta who are three points off the Champions League places.
Zapata, 27, has scored 19 league goals this season, matching Juventus star Cristiano Ronaldo's haul and two behind Sampdoria's Fabio Quagliarella.
Torino held Fiorentina 1-1 in Tuscany and are three points adrift of the Europa League places.
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