So much has changed since the 49ers upset the defending NFC champions, 20-16, in the season opener at University of Phoenix Stadium.
The 49ers' philosophical shift on offense -- the most profound in-season reversal I can recall -- demands the most attention from a long list of changes since the teams met in Week 1. Coordinator Jimmy Raye has channeled his inner Mike Martz since switching quarterbacks, passing the vast majority of the time even in close games. It's a transformation no one could have anticipated to this extent.
This Cardinals-49ers rematch amounts to a last stand for the 49ers. They have lost six of their last eight games in falling to 5-7 and nearly out of the NFC West race. The Cardinals, 8-4 for the first time since 1976, can claim their second consecutive division title by winning this game.
"In my mind, it's not over until it's over," 49ers coach Mike Singletary said.
With that, we take a closer look at 11 significant changes differentiating this matchup from the season-opening one:
1. Alex Smith is the 49ers' quarterback.
They also liked what Shaun Hill was giving them, to a point.
Hill's fourth-quarter leadership was the difference for San Francisco during that Week 1 victory. He passed 13 times during the 15-play winning touchdown drive. But with the offense bogging down by midseason, the 49ers gave Smith another chance to fulfill his first-round draft pedigree.
Their offense is not recognizable from the one the Cardinals faced in Week 1.
2. Steve Breaston is available to the Cardinals.
The Cardinals built their Week 1 game plan under the assumption Breaston would play a more prominent role. Starter Anquan Boldin was the one whose injury status had played most prominently into the coaches' thinking.
That's why Arizona wasn't prepared when Breaston's knee acted up during warm-ups, landing him on the inactive list unexpectedly. Boldin, slowed by a hamstring injury, was limited. The team moved Jerheme Urban, then its fourth receiver, into the "Z" receiver position.
Quarterback Kurt Warner never appeared comfortable.
Warner is looking comfortable. With a strong showing Monday night, he can become the only player in NFL history to post a passer rating of at least 120.0 in five consecutive games.
3. 49ers left tackle Joe Staley could be available.
Staley hopes to return from a knee injury against the Cardinals.
If he does return, he'll face an improved and more seasoned Calais Campbell.
An ascending second-year defensive end, Campbell was making his first regular-season NFL start in Week 1. Campbell has 1.5 sacks in the Cardinals' last two games.
4. Cardinals left tackle Mike Gandy has been injured.
Arizona has valued continuity on its offensive line, but backup left tackle Jeremy Bridges provided an upgrade at the position with a surprisingly strong relief showing against Jared Allen and the Vikings in Week 13.
Gandy, slowed by a pelvic injury, practiced this week. He had been part of an offensive line that started the same players for 31 consecutive games, counting playoffs.
But Bridges looked good against Minnesota. Perhaps Gandy could use another week to recover, if you know what I mean.
5. Crabtree is playing for the 49ers.
The rookie first-round draft choice has produced steadily, if not spectacularly, since joining the team for its Week 7 game against the Texans.
Crabtree has caught between four and six passes in six of his seven games. He has one touchdown grab, a 38-yarder against Green Bay.
Expect a breakout game for Crabtree at some point this season.
6. Isaac Bruce is a non-factor.
The potential Hall of Fame receiver has not been active in three of the last four games.
The 49ers have phased him out.
Bruce, 37, appears to be finishing his career quietly.
7. Ben Patrick is available to the Cardinals.
The starting tight end served a four-game suspension to begin the season.
The Cardinals played 32 snaps with four wide receivers and only nine snaps with two tight ends against the 49ers in Week 1.
Arizona has been using two tight ends far more frequently in recent weeks. Expect that to continue.
The Cardinals used their four-receiver offense 23.4 snaps per game over their first seven games. That has fallen to 13.2 snaps per game over the last five.
8. Vernon Davis is now a legitimate Pro Bowl-caliber tight end.
The Cardinals know the NFL's fastest tight end can hurt them.
Davis caught an 18-yard touchdown pass over safety Adrian Wilson during the teams' Monday night game in Week 10 last season.
Davis has 10 touchdown receptions this season. He has become the best player on the 49ers' offense.
9. The Cardinals are seeking balance.
Arizona averaged 64.8 yards rushing per game in its first seven games. That average has risen to 135 yards per game over the last five.
10. Nate Clements isn't playing for the 49ers.
The 49ers have generally done a good job limiting Fitzgerald's production since Clements signed with San Francisco before the 2007 season.
Clements remains sidelined by injury.
Clements, one of the best tackling cornerbacks in the league when healthy, might also be missed in run support.
11. Gore might be an afterthought.
The former Pro Bowl running back has only 32 carries in his last three games.
The Cardinals will be ready for him in case the 49ers suddenly go back to Gore, but San Francisco appears likely to stick with its passing game.
"We're going to go forward with it and continue to have Alex Smith do the things that he’s been doing, trying to continue to get the timing of the receivers down, getting a rhythm for our offense, finding out what is the right balance," Singletary said, "and we really won’t know what that is until we get into the game and find out how Arizona plans to attack what we’re doing."