An in-depth exploratory study identified major stressors experienced by children diagnosed with cancer. Four themes were used to analyze data from a series of focus group discussions and individual interviews with children, parents, hospital professionals, and hospital teachers (N = 35). First, major stressful events were reported by the children, their parents, and hospital professionals. Second, the effects of major stressors on the well-being of the children, their families, school, and hospital personnel were determined. Third, the children reported the consequences of major stressors on their physical and emotional well-being. Fourth, the children's use of effective coping mechanisms was determined. The results revealed that the major stressors for children with cancer were treatment procedures (e.g., chemotherapy), loss of control, the hospital environment, relapses, and fear of dying. In addition, the children cited body image issues, ongoing lack of self-esteem, and issues relating to the preparation for transition back into real world situations (e.g., school).