Prior to Saturday's showdown, Ronaldo had failed to score or assist a goal in the knockout stages of a World Cup. Before he gave Ricardo Pereira any chance to close him down, Cavani placed a clinical first-time strike back across the goal and into the back of the net.
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It was thanks to his header that Uruguay beat Italy 1-0 in their decisive group game in Brazil to reach the last 16 of the last World Cup and even though they fell to Colombia in the next round, the memory of the goal lives on.
Ronaldo, 33, may have made his final ever appearance at the World Cup.
Uruguay are yet to concede a single goal at the 2018 World Cup, facing just six shots on target in three games - the last South American team not to concede in their first four matches of a World Cup tournament was Brazil in 1986.
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Uruguay have yet to concede a goal in Russian Federation, although going forward they have relied mainly on set pieces to score their goals.
Messi's return in Russian Federation was more meagre - at times he looked disillusioned on the field as Argentine struggled to find anything like their usual style and he drifted deep into midfield in the forlorn hope of influencing games.
His first goal on Saturday involved an incredible, cross-field combination with Luis Suarez.
This is the first time Uruguay have won their opening four games to a World Cup tournament since 1930, with the fourth game in that run being their 4-2 victory over Argentina in the final. KEYS TO THE GAME Stopping Ronaldo.
Ronaldo had company everywhere he went on the field and Portugal's supporting cast was unable to provide enough help.
2 minute: Free-kick to Portugal after Pepe goes down in a challenge from Cavani. They're fortunate to have advanced and need to find a way to capitalize on scoring opportunities to get by a tough Uruguay team.