Sincerely written and performed with an equal degree of affection, “50/50” arrives at the sunset of September to challenge the once-popular notion that autumn is no place for Oscar-caliber work. An out-of-nowhere masterpiece from director Jonathan Levine (who previously brought us 2008’s criminally underseen “The Wackness”), the film pulls off what few before it have even dared to attempt, availing itself of a notoriously touchy subject (cancer) with such lighthearted dexterity as to make creating a comedy of it seem almost effortless. 

Speculation is that screenwriter Will Reiser might see a well-deserved “Best Original Screenplay” nod for his script (originally titled “I’m With Cancer”).

The story, based on Reiser’s real-life battle with cancer, follows diffident radio producer Adam (Joseph Gordon-Levitt), a 27-year-old neat freak whose only knowledge of the word “risk” involves crossing the street without a proper “walk” signal. After being told of his affliction with a rare form of spinal cancer, he enters a staggeringly funny and emotionally charged journey toward happiness and acceptance, ultimately coming face-to-face with death and — in a sequence that should rightfully earn Gordon-Levitt an Oscar nod— acknowledging his fear of it. 

There’s little not to love about “50/50.” One of its best elements is the tear-inducingly genuine relationship between Adam and his best friend, Kevin (played by a surprisingly toned-down Seth Rogen). Anjelica Huston, too, is marvelous as Adam’s overbearing mother, and Anna Kendrick makes for an adorably modest love interest in her portrayal of fresh-faced psychologist Katie McCay. Film experts will also be impressed by the film’s editing, and perhaps even more so with cinematographer Terry Stacey’s understated handheld approach to the material. 

But the real winner (as stated before) is Reiser’s script, which is written with such spirited authenticity that it’s no surprise to hear it’s the result of personal experience. “50/50” draws humor from the most unexpected places, teetering the line between comedy and drama with an almost cheeky sort of confidence that is quite rare among films of this day and age. What we’re left with, then, is a gift: a film that’s as funny as it is genuinely touching, whose only goal is to remind us that, at the end of the day, even in the darkest of circumstances, sometimes the best thing we can do for ourselves is laugh.