BACKGROUND: Children with cancer are reported to experience many symptoms during the cancer trajectory. However, minimal qualitative research has been conducted that explores children’s and families’ experiences of symptoms. An understanding of the symptom trajectory, grounded in children’s and families’ experiences, is essential to providing comprehensive and sensitive care to children with cancer and their families. AIM: This paper reports a study designed to explore and describe the symptom course in childhood cancer as experienced by children and their families. DESIGN: Guided by the philosophy of interpretive interactionism, a longitudinal qualitative study was undertaken. A purposive sample of 39 families of children with cancer who resided in Western Canada participated. The children ranged in age from 4.5 to 18 years and varied in their cancer diagnoses. METHODS: Multiple data collection methods included formal and informal interviewing and participant observation. Data were analysed by the constant comparative method. Development of illness narratives added to an understanding of children’s and families’ experiences. FINDINGS: A substantive theory entitled ‘Children’s and Families’ Lived Experience of Childhood Cancer Symptoms’ emerged from the findings. This depicts the experience of cancer in relation to children’s changing symptom trajectory. A core category of the theory, ‘passage through the transition periods’, shows how changing symptom experiences affected children’s and families’ ways of being in the world. These were reflected in six transition periods: (1) it is just the flu; (2) it is more than the flu; (3) it hits home; (4) it is nasty; (5) it is not so bad, it is pretty good; and (6) it is ‘dragsville’. The changing roles and responsibilities of family members, and how the family existed in the cancer world, varied depending on the transition period through which they were passing. CONCLUSIONS: Transition periods not only reinforce the dynamic nature of the experience of childhood cancer but, more importantly, show how symptoms can greatly affect the quality of children’s and families’ day-to-day living. Interpreting cancer in the context of the symptom trajectory provides nurses with a new perspective for understanding childhood cancer, and will assist in the development of symptom relief strategies that will help to contain symptoms and improve overall quality of life for children and families.