Spiller, who had 58 total yards and touchdown, looked primed for another huge day before falling hard on his shoulder during a screen play that ultimately was called back due to a holding penalty.
Next in line for Buffalo?
Former Dallas Cowboys runner Tashard Choice.
Let's break down what Spiller's injury means from a fantasy perspective and the ripple effect it'll have on the Bills' offense in the foreseeable future.
Spiller came into the Week 3 contest with the Browns as the hottest fantasy start at the running back position.
Okay, Reggie Bush owners may disagree, but you get the picture.
The former Clemson stud was leading the NFL in rushing with 292 yards and was averaging more than 10 yards per carry in the Bills' collegiate style spread offense.
With Fred Jackson injuring his knee against the Jets, Spiller was undeniably making the most of his opportunity as Buffalo's featured runner.
Head coach Chan Gailey stated after the game that Spiller did not break his collarbone, as many speculated (according to WGR 550 radio out of Buffalo).
Chan Gailey says CJ Spiller will likely miss next week vs. New England, but does not expect Spiller to miss much longer— WGR 550 (@WGR550) September 23, 2012
It's highly unlikely that Spiller will be able to go next week against the New England Patriots in Buffalo, and Jackson, according to the team's official website, has "a chance" to return when Tom Brady and Co. come to town.
So, Spiller has to be sent to the bench for the time being, and Jackson's availability should be monitored for Week 4. Choice has to be a consideration as a waiver-wire addition, as he's likely to get the lion's share of the carries until both runners are nursed back to full health.
Spiller was finally playing the way the Bills hoped he would when they drafted him with the No. 10 overall pick, running with the vision, decisiveness and tremendous burst he demonstrated during his illustrious career at Clemson.
Ryan Fitzpatrick can be serviceable at times, but Buffalo's offense runs much more efficiently when the running game keeps him out of precarious situations.
If Spiller and Jackson can't go for the next few weeks, the Bills will be forced to tweak their offensive game plan, but don't be shocked if it doesn't change dramatically. The offensive line has dominated through three games, and Choice is a veteran in whom Gailey has a great deal of confidence.
However, there's no doubt about it—the Bills will be far less explosive as an offense without Spiller in the lineup. The receiving corps is already a weakness, and the Buffalo coaching staff hasn't displayed any faith in the wideouts to stretch the field at the start of the season.
With the Patriots and 49ers next on the schedule, the Bills may have to rely on Fitzpatrick, a guy who had a solid game against the Browns in Week 3.