Napoli had a goal disallowed for offside in the 80th.
But Real were level, against the run of play, seven minutes later, when Karim Benzema powered home a header from Dani Carvajal's cross. Napoli who are unbeaten away from home in this year's competition and are arguably playing the best football in Europe right now, are also unbeaten in all competitions since October winning 11 out of 13 games.
When is the second leg?The former Real Madrid wideman is Napoli's second top scorer domestically and is offered at 13/5 (3.60) to net on his return to the Bernabeu.
Real Madrid boss Zinedine Zidane has resisted the temptation to rush back a fit-again Gareth Bale their Champions League clash today against an on-form Napoli backed by Diego Maradona.
Real Madrid had a minor blip in January, when they lost two games in a row and were knocked out of the Copa Del Rey by Celta Vigo.
In the other Round of 16 game on Wednesday, Bayern Munich routed Arsenal 5-1 in Germany.
At that point it looked like it could be a long evening for Napoli, but the Italians were in no mood to lie down and took the lead to cap a frenetic opening after eight minutes. It was soon 3-1 when Casemiro smashed a 25-yard volley across a helpless Pepe Reina and into the far corner. "Maybe we made too many mistakes, this will only push us to work even more".
Toni Kroos then gave Real Madrid the lead in the 49th minute after Cristiano Ronaldo beat his defender and set up the German for a low effort to the front post.
Dries Mertens spurned a fantastic opportunity on 68 minutes, dragging a shot high and wide from Jose Callejon's close range cutback.
The star forward remains two goals short of becoming the first player to score 100 goals in European competitions.