"We almost look like brothers," Rel, whose real name is Milton Howery, said. "I'm way more handsome than him, so I know it's the glasses."
But that's where the similarities end, as both comics told RedEye in separate interviews. Their acts are seemingly polar opposites, making them something of a comedy odd couple. Fans can see that for themselves with Buress performing at Zanies Comedy Club this week and Rel continuing to perform all over the city, including at Jokes & Notes Comedy Club in Bronzville on Wednesdays.
On stage, Lil Rel is fast-talking and animated, using for his material experiences from the West Side such as life with his parents and 'hoodrats on the bus, while Buress is observational, cerebral and popular with hipsters, telling stories about his desire to kick pigeons or not waste pickle juice.
The differences in their personalities are apparent face-to-face, with Lil Rel talking excitedly while Buress speaks slowly and directly.
While calling Buress' comedy "our generation's Jerry Seinfeld," Rel admitted his style was much different. "I'm a little more ghetto than he is," Rel said. "That's what makes our relationship unique. We're nothing alike."
Against the odds, the two grew up on the West Side and decided to try comedy.
"To think about where we're at in comedy and where we're from, it's fascinating," Rel, 31, said. "Not even just comedy, two guys from the West Side to make it all the way through with something."
They both got their starts going to open mics in college, with Rel attending Harold Washington College and Buress going to Southern Illinois University.
"It was something I hadn't thought of doing until I started going to open mics about a month before," said Buress, 28, who now lives in Brooklyn. "And there were some bad people at the open mics, so I decided to try it."
Their paths soon crossed. Buress' second time on stage, he opened a show Rel was headlining at SIU. They recognized a mutual seriousness about comedy and bonded. Especially, Rel said, once he found out Buress had a "terrible" Ford Escort.
"I didn't have a car at the time, so I used to follow whatever comic had a car … and let them open up for me," Rel said. "He had the worst car in the world. I remember thinking, 'This is not going to work.' I don't know how we got to Peoria."
After driving to gigs together on the South Side for a while, Rel suggested Buress work the North Side comedy clubs.
"With Chicago, the style of comedy is segregated," Rel said. "Sometimes with the urban rooms they want the style fast and aggressive. His style is a little chill. You have to hear him out to know what's going on. So I was like, 'You got to go up north. Don't keep trying to fight with these people.'
"And he did and he dominated. He was like the king up there."
Since then, Buress' career has taken him a long way from beat-up Ford Escorts. In 2008, he moved to New York. After a year, he was hired to write for "Saturday Night Live."
"It was great to have that job, but I don't think it was extremely crazy," Buress said. "I'm not famous and that didn't make me famous; it just kind of gave me a better credibility within the industry and made me more well-known in comedy circles. It was a job, it was fun."
He left "SNL" to write for "30 Rock" in 2010, and this season had a recurring role as a homeless guy. He recently quit "30 Rock" to focus on stand-up and write his own show, but that is "super preliminary," he said.
Meanwhile Rel, who lives in the south suburb of Harvey, has had his own share of success, appearing on "Last Comic Standing," among numerous other TV spots. He has been flying to L.A. for his budding acting career after starring in the film "Get a Job" last year.
The two stay in touch. In interviews, Buress frequently mentions Rel as one of his favorite comedians. But don't expect to see them perform together.