Edin Dzeko hit a hat-trick for Roma - and became the leading scorer in this season's Europa League - in a 4-0 last-32 first-leg win at Villarreal.
The former Manchester City striker, 30, scored three in the last 25 minutes to take his European total to eight goals.
It put him one clear of Athletic Bilbao's 36-year-old striker Aritz Aduriz, who was on target in a 3-2 first-leg home win over Apoel Nicosia.
Klaas-Jan Huntelaar, another veteran at 33, scored as Schalke won 3-0 at PAOK.
There was controversy in Poland, where Ajax appeared to be denied a legitimate goal in a 0-0 draw at Legia Warsaw.
Arkadiusz Malarz, the Legia keeper, seemed to pull back Ajax captain Davy Klaassen's eighth-minute shot from behind the line, but none of the officials saw it go in - and there is no goalline technology in the Europa League.
A gloomy fortnight for Celta Vigo continued as they lost 1-0 at home to Shakhtar Donetsk, with Gustavo Blanco scoring the only goal.
The La Liga side had to postpone a home game against Real Madrid just under two weeks ago after their stadium suffered storm damage. They then lost a Copa del Rey semi-final to Alaves before conceding two goals in the last four minutes to fall to a 3-2 league defeat at Atletico Madrid last Sunday.