The top teams in Group G meet on Saturday evening in a game which could decide which of the two gains an automatic place at next summer's World Cup.
Spain lead Italy on goal difference with both sides on 16 points and last October they played out a 1-1 draw in Turin. Another stalemate this weekend would leave the group even tighter, while both teams know that a victory would see them take a huge step towards automatic qualification.
The Bernabeu in the Spanish capital is a fitting setting for what should be an intriguing match between two old rivals, and bet365 offer the hosts at 17/20 (1.85). History dictates a close clash, with La Roja having never lost a home World Cup qualifier - an incredible record that they share with the Italians.
The Azzurri, however, will provided the sternest opposition that Spain have faced in a competitive game on home soil since France visited in 2012, and the visitors are offered at 17/4 (5.25) to claim what would be a historic victory. The draw, meanwhile, is offered at 12/5 (3.40) and four of the last seven meetings between the two sides have ended as stalemates.
The two sides are evenly matched and defensively strong, yet the price of 11/10 (2.10) for goals at both ends catches the eye. Italy have only failed to score in one of their last 23 World Cup qualifiers, and while they will face a tough unit at the Bernabeu, they have the capacity to find the back of the net.
Spain, for their part, have scored in every home World Cup qualifier they have contested since November 1992 - a run of 31 games - and punters should feel confident that Julen Lopetegui's men will get themselves on the scoresheet once more.
For higher odds, backing both teams to score in the second half at 10/3 (4.33) is an excellent option for a value bet. With plenty on the line, expect a tight opening, yet the second half could well yield goals as the sides look for the win and this selection proved profitable in the last meeting 11 months ago.