Two days after his acrobatic skills saved Italy's blushes against unfancied Armenia, Buffon was seen going into a physiotherapist's clinic on Sunday to receive treatment on what a team official said was a left thigh injury.
Italy won 3-1 in Yerevan thanks to second-half goals from Daniele De Rossi and Pablo Osvaldo but could easily have lost to a spirited Armenia side had Buffon not saved them following some sloppy defensive errors.
If the Juventus keeper is sidelined for Tuesday's encounter at the San Siro, it could dent Italy's chances of maintaining their place at the top of Group B.
Prandelli, who has lined up Napoli's Morgan De Sanctis as Buffon's replacement, has other problems in defence, with Leonardo Bonucci the worst of a back-line which gave away far too many chances on Friday.
Neither he nor Domenico Criscito, making his return to the national team since being kicked out of the Euro 2012 squad as part of match-fixing investigations, ever looked comfortable in the centre of the defence.
On Saturday, Prandelli said that Juventus centre-back Giorgio Chiellini would be selected to stand up to the physical Danish striker Nicklas Bendtner, who scored Denmark's equaliser against 10-man Bulgaria on Friday.
There are also issues in attack, with indecision over who is the best partner for in-form Roma striker Pablo Osvaldo, who has scored six goals in six matches for club and country this season.
With Mario Balotelli ruled out of the Armenia match with influenza, Sebastian Giovinco failed to impress on Friday and limped off with an ankle knock.
Manchester City striker Balotelli trained on Saturday and could feature for the first time since Euro 2012 if he recovers in time, although Milan striker Stephan El Shaarawy has been kept on standby.
Denmark, who are fifth in the six-team group with two points, cannot afford another slip-up following a disappointing 1-1 draw in Sofia.
"We need a result in Italy, there is no doubt about that, and we can take some of the good things from the second half here in Bulgaria. I am also confident that we can get something from there," Ajax midfielder Christian Eriksen told TV6.
Teams (probable):
Italy: 1-Morgan De Sanctis; 2-Christian Maggio, 3-Giorgio Chiellini, 4-Domenico Criscito, 15-Andrea Barzagli; 8-Claudio Marchisio, 16-Daniele De Rossi, 18-Riccardo Montolivo, 21-Andrea Pirlo; 17-Pablo Osvaldo, 9-Mario Balotelli.
Denmark: 1-Stephan Andersen; 2-Tomas Kristensen, 3-Simon Kjaer, 4-Daniel Agger, 23-Patrick Mtliga, 6-Lars Jakobsen, 7-William Kvist, 8-Christian Eriksen, 9-Michael Krohn-Dehli, 10-Dennis Rommedhal, 11-Nicklas Bendtner.
