The protagonist, 12 year old, Rob Horton, recently moved to Florida and is having a hard time adjusting to his new life. He is still struggling with the death of his mother, all the while being bullied by boys at school, and dealing with a rash on his legs. Thinking about the tiger he saw one day on his way to school, helps distract Rob from the negative things in his life.
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On the way to school one morning, Rob notices a girl who he has never seen before, get on the school bus. This girl, Sistine Bailey, seems different than the other girls at school, and when she was also taunted by the same bullies as Rob, she defends herself. This surprises Rob, so he becomes curious about her.
Rob continues to notice how Sistine is different from the other kids at school. On the bus, Rob and Sistine talk and begin to share information about their lives. Hesitantly, Rob opens up about the bullies and the rash on legs, but he does not tell Sistine his secret about finding the caged tiger days prior.
One morning, the principal informs Rob that he must stay home for awhile in order to treat the rash on his legs. Rob is thrilled because he doesn't want to go to school anyway. During this time, Rob helps his dad with his maintenance work at the motel, and Sistine brings Rob his homework, and their friendship builds. Eventually, Rob opens up about his past and even tells Sistine about the caged tiger.
One day, while working around the motel, Rob's father's boss, Beauchamp, tells Rob that he has a new, secret job, which is to feed the caged tiger. Beauchamp shows Rob the tiger, and Rob becomes increasingly worried for the tiger's wellbeing based on how Beauchamp spoke of it, as if it was only worth money to him. Rob knew he needed to tell Sistine that he had the keys to the cage.
After Rob told Sistine about the keys, she is adamant that they need to set the tiger free. Rob is worried because he made the business deal with Beauchamp and promised to keep it a secret, but he also feels bad for this tiger and cares about his friendship with Sistine. Does he agree with Sistine and free the tiger, even though that could be a dangerous situation with Beauchamp? Or does he continue to uphold his deal?