50/50 is a serious-minded comedy about cancer, and writer Will Reiser and director Jonathan Levine's greatest accomplishment is that it starts out being a good movie in spite of that premise, and ends up being a great one because of it. That's a neat trick, if you can get away with it. It disarms you with its irreverence and candor; it distracts you with a romantic subplot that shouldn't work, but does. And then, at its conclusion, it reveals itself as a genuinely emotional heartbreaker, and it wrings you out. Resier and Levine are a couplea sneaky bastards.

Joseph Gordon-Levitt and Seth Rogen play (respectively) Adam and Kyle, longtime friends and co-workers. Adam is a straight-laced dude; he doesn't smoke, doesn't drink, and has a live-in artist girlfriend (Bryce Dallas Howard) who he's too nice to ask for sex from. And then he gets the big C. The reveal of the disease is one of the picture's strongest moments; it expertly captures the very specific way you stop listening to a doctor after they say a phrase like "Your cancer is..."

But his cancer is rare, especially in a 27-year-old. He has, he is told, about a 50% chance of survival, with chemotherapy treatments and the possibility of surgery. He immediately dreads telling his overprotective mother (Anjelica Houston), and he decides the best way into the conversation is to ask her, "Have you ever seen Terms of Endearment?" Adam gives the girlfriend an out, but no decent person wants to actually take that out, so she sticks around as long as she can, even though she doesn't want to go to the hospital with him; hospitals freak her out. Kyle lands on two coping strategies, almost immediately: medicinal marijuana, and trying out cancer as a pick-up device.

Reiser's screenplay, written from his own experience, mostly focuses (wisely) on the small stuff, the logistics and day-to-day details of the disease. He goes to chemotherapy, and befriends two cancer patients who are, unsurprisingly, far older and wiser (Philip Baker Hall and Matt Frewer flesh out the already impressive supporting cast). As part of the treatment, he sees a therapist, played by the always-delightful Anna Kendrick. She is 24 (it's a teaching hospital); he asks if she's some kind of Doogie Howser, and then has to explain that Howser is a teenaged doctor. "Does he work here?" she asks.

This is the kind of bright but vulnerable character that Kendrick does so well; watch the wonderful dodgy manner with which she answers his questions about how many previous patients she's had, or the careful way she handles a desperate telephone call that leads to Gordon-Levitt's most powerfully raw moment. It should no longer come as a surprise that he's good in a film--he is always good, in everything (a statement that I shall preserve by never seeing G.I. Joe), but he plays every beat of his character's clear and well-defined arc with both precision and spontaneity. He and Rogen prove a good on-screen duo, sharing a tight conversational cadence and a sense of shared history. Rogen proves, unsurprisingly, to be the film's "comic relief," but he does so unapologetically, and the picture is better for it; when he informs a doctor that "You should start with that information," it punctures the tension beautifully.

Yet and still, in mere description, 50/50 sounds like a movie-of-the-week, and in all fairness, it occasionally verges on that territory. But Levine (whose previous picture, The Wackness, was a bit of a crowd-splitter), mining the skills of his tremendous cast and Reisner's smart screenplay, and maximizing a top-notch soundtrack without merely relying on it, keeps it all aboveboard. It's not a showy movie; it's quiet and personal, its events working towards small-scale climaxes. As a result, it is that rarest of creatures: an honest tearjerker, in which the emotions are earned rather than manipulated.

Jason lives in New York. He holds an MA in Cultural Reporting and Criticism from NYU.