Movies about Gen Y don’t usually tackle anything as sordid and, frankly, as creaky and unhip as cancer. The ultimate buzz kill, the Big C tends to detract from the pop-culture jokes and childhood nostalgia in your average mumblecore chat stew.

In some sense, though, it seems like just about time for a Gen Y cancer comedy, and director Jonathan Levine’s 50/50 is it. Movies for millennials have been slowly easing them into adult “issues” like relationships, job loss, and even marriage and babies. Can the first navel-gazing film about menopause or infertility be far behind?

Part of what makes 50/50 a heartfelt step above the usual disease-of-the-week melodrama is how it incorporates the ethos of its generation. When 27-year-old Seattle public radio journalist and neat freak Adam (Joseph Gordon-Levitt) breaks the news of the cancer growing on his spinal cord to his best friend Kyle (Seth Rogen), Kyle sees it as a chance to score some sympathy sex from every nearby babe. A Judd Apatow sidekick from central casting, Kyle is a prototypical lad-man: He lashes out at women even as he longs to sleep with them and mistakes cursory man-hugs and drunkenness for “relating.”

Adam’s co-workers are equally clueless. At a going-away party at his radio station, the assorted PC-sensitive types look past Adam, clearly anxious to wrap up the sympathizing and get back to the keg. Adam’s sexy artist girlfriend Rachael (Bryce Dallas Howard) “forgets” to pick him up for his post-chemotherapy ride home, quickly discarding her Florence Nightingale promises to nurse him through the illness.

The people who seem most sympathetic are older and wiser. These include Adam’s mother Diane (the always delightful Anjelica Huston), who is already caring for Adam’s Alzheimer’s-afflicted father and two other middle-aged cancer patients, Alan (Philip Baker Hall) and Mitch (Matt Frewer), who become his chemo-buddies. Alan and Mitch share their pot brownies and invite Adam to backyard barbecues with wheatgrass shooters. These, the film makes clear, are people to whom life has probably dealt a fair share of misfortune, unlike Adam’s wound-free peers. With no relatable hard times of their own, 50/50 suggests many of Adam’s friends are emotionally stunted.

Based on writer Will Reiser’s own real-life cancer diagnosis, 50/50‘s critique is not just generational; the film also offers a mild scorching of the American healthcare system. Delivering the news of Adam’s cancer, his doctor sits down at his desk to read the diagnosis into a tape recorder while Adam sits across from him, gobsmacked. Instead of exhibiting any form of sympathy or bedside manner, his doctor essentially outsources his compassion, hooking Adam up with a fidgety, insecure disease counselor Katherine (Anna Kendrick), new to the job and open about her inadequacies and anxieties.

It turns out that death sucks either way, but having to face it while your friends are cracking jokes and your girlfriend is eyeing the next guy in line makes it even harder to stomach. It’s a truth most disease-yarns don’t have the guts to speak: sometimes people let you down, are selfish, and disappear.

50/50 is a little sitcom light and can take the conventional road on more than one occasion. The film’s disdain for the contemporary art beloved by bad girlfriend Rachael, for instance, is positively fogeyish, and something you’d be more likely to find in a vintage Woody Allen film.

But the film hangs together despite itself because of the chrome-dome appeal of indie wunderkind Gordon-Levitt. Beneath even seemingly disparate performances — as a death-metal anti-hero in the cyclonic, crazed Hesher or the sensitive cancer dude in 50/50 — Gordon-Levitt always suggests an actor with his heart in the right place and an urgent need to remind viewers of all the pain and tumult beneath the surface of things. An old soul, he seems to have always had an intuitive understanding of what really matters, and that cumulative sense of integrity and grit comes through once again in this memorable performance.