The tie is far from over however, and should they secure an early goal the hosts, at a sold out Stadio San Paolo, will feel they have the firepower to secure a place in the quarter finals of the Champions League for the first time in their history.
In the first leg it was Lorenzo Insigne who opened the scoring with an audacious long-distance effort which caught Real Madrid goalkeeper Keylor Navas off guard, and the Italy international is offered at 2/1 (3.00) to find the net once more.
Our tip for the first leg was backing Karim Benzema to score at anytime and Madrid's number 9 duly obliged with the equalizer to keep up his superb record in the competition.
With 51 goals in the Champions League, Benzema is the tournament's fifth highest scorer of all time and has found the back of the net in each of his last four games in the competition.
The price of 7/5 (2.40) for him to do so once more surely can't be ignored especially after his excellent performance at the weekend where the 29-year-old scored twice in the 4-1 win at Eibar.
Napoli also boast an in-form striker who scored twice at the weekend with Dries Mertens' brace helping Maurizio Sarri's side to a hugely impressive 2-1 at Roma. Mertens picked up a knock in the game but looks likely to be available for the clash on Tuesday with the Belgian offered at 6/4 (2.50) to find the back of the net at anytime.
Only Benzema and Cristiano Ronaldo are ahead of the 29-year-old in the betting with the most successful goalscorer in Champions League history offered at 3/4 (1.75) to find the back of the net.
Ronaldo did not manage to score in the first leg, but he did score the last time Madrid faced an Italian side in Italy, with his strike against Roma in the last 16 of last year's competition named the goal of the tournament by UEFA.
Elsewhere Gareth Bale can be backed at 17/10 (2.70) to add to his tally of two European goals this season, while Napoli captain Marek Hamsik can be backed at 2/1 (3.00) and Jose Callejon is offered at 19/10 (2.90) to net against his former side.