While the suspension of Luis Suarez deprives Uruguay of their best player and record scorer, La Celeste can draw hope from the success of last-16 opponents Colombia.
Los Cafeteros lost star striker Radamel Falcao to injury before the tournament began but have been anything but toothless in attack.
Conventional wisdom dictated that the absence of Falcao, who scored nine of their 27 goals in qualifying, would leave Colombia lacking a ruthless touch in front of goal.
Instead they scored nine goals in three group matches, with their shot conversion rate (31%) the best of any team in the first phase of the tournament.
Shot conversion, group stage of 2014 World Cup Colombia 31% Netherlands 29.4% Algeria 25% Germany 24.1% Chile 22.7%
Falcao's injury prompted coach Jose Pekerman to switch from a 4-4-2 formation to 4-2-3-1. So far that system has given more creative license to outstanding attacking midfielders James Rodriguez and Juan Cuadrado, who have five goals between them in Brazil.
The Colombians scored more goals than the three other teams in Group C combined, but they face a real step-up in class against the streetwise and experienced Uruguayans.
The only previous World Cup match between the sides was won by Uruguay in 1962, when the victors were coached by Juan Carlos Corazzo - the grandfather of current striker Diego Forlan.
Uruguay have also enjoyed the better of recent encounters, winning six of the last eight meetings. That includes Colombia's most recent defeat, a 2-0 loss in a qualifier in Montevideo on 10 September 2013.
On that occasion Edinson Cavani headed the decisive goal. The Paris St-Germain striker often plays second fiddle to Suarez for Uruguay, but he will be a key man on Saturday.
Play mediaThe Uruguayans may draw inspiration from playing this game in Rio, scene of the greatest win in their history.
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Alcides Ghiggia's winner against Brazil in the final game of the 1950 tournament famously silenced the Maracana.
Saturday's atmosphere may not be quite so partisan, yet the travelling Uruguayan fans are likely to be greatly outnumbered by their Colombian counterparts and most neutrals can be expected to side with Pekerman's adventurous team.
That will only serve to inspire the Uruguayans. Victory for La Celeste would not match the shock value of the "Maracanazo", but would be almost as satisfying for a team convinced they have been unfairly treated by Fifa.
- Colombia's first World Cup match was a 2-1 defeat by Uruguay in Chile in 1962.
- That is the only previous occasion the sides have met at a World Cup, and is also Colombia's only previous meeting with South American opposition.
- In the last 10 years, Uruguay have won six of their eight games against Colombia (D1, L1).
- Colombia's only win in that sequence was by 4-0 in a World Cup qualifier in Baranquilla in September 2012. The Uruguayans won the return fixture 2-0 in Montevideo a year later.
- Los Cafeteros are unbeaten in their last 10 games (W6, D4) since losing 2-0 in Uruguay last September.
- Colombia lost their only only previous World Cup knockout game 2-1 to Cameroon in 1990.
- They have won as many World Cup matches in Brazil (three) as in their previous 13 tournament games combined.
- James Rodriguez has scored in his last five appearances for Colombia, including all three World Cup matches.
- He has scored three goals and assisted two more in 225 minutes in Brazil - which equates to scoring or assisting a goal every 45 minutes.
- Nine of Colombia's last 11 goals at the World Cup have been scored in the second half of matches.
- Uruguay have not beaten South American opposition in a knockout World Cup match since victory against Brazil at the Maracana in 1950. That match was the de facto final as it was the last game in the final round, with Uruguay needing a win to clinch the title.
- They have scored in each of their last nine World Cup games - the last time they failed to find the net was in a 0-0 draw against France on 11 June 2010.
- La Celeste have lost the last two World Cup games Luis Suarez has missed: 3-2 against Netherlands in 2010 and 3-1 versus Costa Rica in their opening match in Brazil.