Miss Smilla's Feeling for Snow (in Danish, Froken Smillas fornemmelse for sne; published in America as Smilla's Sense of Snow) is difficult to categorize. It can be called a thriller, but not a typical one: it has a plot full of suspense, a murder inquiry and a mysterious romance, but it also raises socially important questions on post-colonialism, alienation and social inequality.

The story begins when Smilla Jaspersen, a 37-year-old single woman of half-Greenlandic, half-Danish parentage, discovers that her young neighbour, an Inuit boy named Isaiah, has died falling off a roof. As the police, convinced it was an accident, rush to close the case, Smilla grows more and more suspicious and starts her own private investigation. She can't believe her little friend, who suffered from a fear of heights, would choose to play on the roof. Besides, as a professional in snow and ice matters raised in a hunting community in North Greenland, she can read footprints in the snow: she concludes that Isaiah didn't fall but jumped off the high roof.

Her promise to Isaiah that she would never abandon him launches her straight into a complicated plot involving rich and unscrupulous people for whom a child's life is inconsequential in the hunt to realise their goals.

Smilla tracks down various people in Copenhagen connected to Isaiah and his mother, explores bizarre clues and seeks help from doctors and policemen. Her father is a rich anaesthesiologist who knows some useful people; despite their bad relationship, he helps her as much as he can in the hope it will bring him closer to her.

Smilla acquires an ally in the form of another neighbour, Peter Føjl, whom she calls "the mechanic". Føjl also befriended Isaiah, and is equally concerned about his mysterious death. Although they don't really trust each other, Smilla and the mechanic begin an affair which leads the always cool and distant Smilla to fall in love.

Smilla and the mechanic discover that two years before Isaiah's death, his father was killed in a strange accident during an expedition to North Greenland. The same company, the Cryolite Corporation Danmark, was involved in another expedition to the same place 25 years earlier and at that time more people died. Substantial amounts of money were involved, and Isaiah was picked up every month and taken to the hospital; Smilla knows she is on the right track.

When she finds out that another expedition is being organised, she decides to join it. She manages to get a job as a cabin attendant on the expedition ship, and sets off to Greenland with a crew of former criminals, drug addicts and broken gamblers. The ship is not a safe place for a woman seeking to uncover the truth, but she doesn't stop searching. She almost gets killed – the second attempt on her life.

Smilla comes to the attention of Tørk Hviid, the brain behind the plot and the man who caused Isaiah to jump from the roof. He plans to dispose of Smilla in Greenland. Worse, her beloved mechanic turns up on board, a collaborator of Tørk and his allies. Nevertheless she still loves him and turns to him anyway; there is no one else she can trust.

When they reach their destination, remote Isla Gela Alta off the north coast of Greenland, Smilla finally discovers the truth: in an ice cave in a glacier lies an ancient meteorite which possesses rare and valuable chemical traits. In the surrounding waters resides a mutated species of parasite, which kills people within days. Tørk is determined to transport this meteorite to Europe, no matter what health risks it involves, as it will bring him money, fame and power. The mechanic, an experienced diver, is needed to help extract the meteorite from the hazardous infected water. 

Tense action marks the end of this chilling, thrilling story, with a final confrontation between Smilla and Tørk on the thin, deadly ice of Greenland's north coast.