La Celeste defeated both England and Italy to finish second in Group D and face a side they have consistently got the better of over the last few years.
Yet despite winning five of their last eight games with los Cafeteros, Uruguay are the outsiders here, with Paddy Power pricing them at 13/5 (3.60) for the win.
That is in large part down to Colombia's form in the tournament so far, having notched three wins from three and scoring nine goals in the process.
They are an adventurous, talented side and many will be rushing to invest in the price of 23/20 (2.15) for them to win.
That price looks even more tempting when you consider that Uruguay are to be without Luis Suarez. When the Liverpool foward is not in La Celeste's starting line-up they certainly lack bite, as demonstrated in their opening clash with Costa Rica.
Indeed, Oscar Tabarez's men have relied heavily upon the striker and while Edinson Cavani remains a huge presence in attack, the Paris Saint-Germain player is at his best when linking up with Suarez as shown during Uruguay's win over England.
Therefore, backing Colombia makes sense. They are full of goals and full of confidence, while Uruguay will be missing their best player and the man most likely to cause the Colombians problems.
In qualifying for Brazil 2014, Uruguay netted 25 goals, 11 of which were scored by Suarez. His absence will be a massive blow for Uruguay not only because of his goalscoring prowess but also the confidence that his talismanic presence brings to the side.
Colombia are priced at 4/7 (1.57) to advance to the next round but bolder punters should take the price of 23/20 (2.15) for them to win in 90 minutes.
|Colombia to win at 23/20 for a 3pt stake with Paddy Power|
Sign up with Paddy Power for up to £250 in free bets and back Phil's selection for this match
Phil Kitromilides is a sports journalist and TV presenter in Madrid