Smilla Jasperson, thirty-seven years old, a physicist, of Danish father and Eskimo mother, lives alone in Copenhagen, without family, without a job, without friends. Her disconnect with her father's world, European civilization and its values, leads her to consciously choose a life on the margins. The only person she feels connected to is Isaiah, a six-year-old Eskimo, a stranger and misfit like herself in Danish society.

One day, Isaiah falls from a snowy roof and dies. The police rule it as an accident and close the case. But Smilla, who saw the child's footprints in the snow and knows how to decipher them, has reasons to suspect something different: murder. She tries to explain her suspicions to the police, but no one seems to care.

Alone, relying solely on her intelligence, instinct, and determination, she struggles to uncover the truth behind her little friend's death and eventually realizes that her own life is in danger. The increasingly dense mystery she delves into will ultimately lead her to Greenland, the country of her childhood.

Peter Hoeg presents a kaleidoscopic image of the modern world, from the perspective of a sensitive and restless individual torn between different cultural traditions, longing for the lost solidarity among people.