Napoli came away from the San Siro with a 2-1 victory over AC Milan with goals from Miguel Britos and Gonzalo Higuain, while Mario Balotelli failed to convert a penalty kick for the first time in his career.
Roma beat rival Lazio 2-0 in the city derby, with fullback Federico Balzaretti scoring the decisive goal and the Giallorossi's 36-year-old captain Francesco Totti again proving decisive.
In the lunchtime fixture, Diego Milito scored twice on his return from injury as Inter thrashed its recently promoted opponent amid news that Indonesian businessman Erick Thohir is closing in on a takeover of the club.
Through four rounds, Napoli and Roma are two points ahead of Juventus, Inter and Fiorentina.
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In Milan, Britos put Napoli ahead six minutes in with a header following a free kick and Higuain doubled the lead in the 53rd with a long, low shot that Rossoneri goalkeeper Christian Abbiati got a hand on but wasn't able to stop.
Balotelli was unfortunate again in the 71st when he hit the crossbar, although he finally found the target in added time with a splendid, curling, long-range effort. Still, Milan dropped eight points back.