Romo suffered a fractured left clavicle in the second quarter of the Cowboys' 41-35 loss to the New York Giants at Cowboys Stadium.
Romo said he will undergo tests to determine the damage, but Cowboys owner and general manager Jerry Jones said the quarterback could miss six to eight weeks.
"We'll see if surgery is required," Jones said. "If not, he's going to have some time out. [Troy] Aikman was out four weeks with this and our [trainers] initially think six [weeks], possibly as long as eight [weeks], but we'll see what his examination is."
The Cowboys, who fell to 1-5, have 10 weeks remaining in a season that has gone haywire.
When Romo went down, the Cowboys were leading 10-7 and seemed to have everything going their way. But after Romo was injured, the Giants went on a 31-10 run to take a 38-20 lead going into the fourth quarter.
"We stayed on the field a lot, and the three-and-outs hurt us a little bit," Cowboys inside linebacker Bradie James said. "But when your starting quarterback gets knocked out, that's why they make the big bucks."
Romo was hurt with 12:07 to play in the second quarter after completing a pass to wide receiver Miles Austin. Romo was hit by Giants weakside linebacker Michael Boley, who came on a blitz. Romo's left shoulder crashed into the turf as Boley tackled him to the ground.
"When he hit the ground, I heard he let out a little scream," Boley said. "So I knew something was up. But I didn't think he was going to lay down. I thought it was just a normal hit."
Romo lay on the field for several moments as a team of trainers and doctors attended to him. Romo's best friend on the team, tight end Jason Witten, along with rookie wide receiver Dez Bryant hovered over their quarterback.
"I tried lifting my shoulder and it hurt like heck, but I was like, OK, it will just keep getting better," said Romo, who suffered the same injury to his right shoulder when he was a teenager. "The adrenaline of the game will allow me to [play], it's my left shoulder, I don't need to use it too much. I will figure out a way what I can handle when I'm out there, but that was before I knew it was broken."
Romo said it was hard to breathe when he was on the field. After he was helped to the sidelines, he tried to re-enter the game with 11:18 left in the second quarter, but associate athletic trainer Britt Brown pulled him back and Romo slowly walked to the bench area.
Surrounded by several trainers and team doctors, Romo was taken into the locker room for further examination, and it was determined he suffered a fractured clavicle.
"I just couldn't move without it really being painful in the shoulder," Romo said. "I was just having a hard time just breathing. ... At a certain point you're like, OK, then something is wrong -- I just know I'm not myself. It's disappointing when you're in that situation."
Romo finished the game 5-for-7 for 39 yards with one touchdown, a 4-yard pass to Witten in the first quarter.
In 2009, Romo was the first quarterback in franchise history to be on the field for every offensive snap. It's that durability that gave the organization confidence it could keep 38-year-old Jon Kitna as Romo's backup.
The last time Romo missed a game due to injury was the 2008 season, when he broke a pinky and missed three games.
When Kitna took over for Romo on Monday night, his first pass was knocked down. It was Kitna's first snap since Oct. 5, 2008, when he played with the Detroit Lions.
His first series ended with a field goal that stretched Dallas' lead to 13-7. The Cowboys were losing 24-20 at halftime.
Romo returned to the bench at the start of the second half, his left arm in a sling and covered by a jacket. He also wore a headset to stay in tune with the game. When Dallas' first series fizzled, he discussed what went wrong with Kitna and looked over pictures of the plays with third-stringer Stephen McGee. He then stood alone and watched the offense go back for its second try.
The Cowboys also lost defensive end Jason Hatcher to a groin injury.