BACKGROUND: The medical traumatic stress model is commonly applied to childhood cancer, assuming that the diagnosis of cancer is a traumatic event. However, to the authors’ knowledge, little is known regarding what specifically children perceive as stressful about cancer or how it compares with other stressful events more often experienced by children. METHODS: Children with cancer (254 children) and demographically similar peers without a history of serious illness (202 children) identified their most stressful life event as part of a diagnostic interview assessing for symptoms of posttraumatic stress disorder (PTSD). The events identified as most stressful were categorized thematically, with categories established separately for cancer-related and non-cancer-related events. Events also were examined to assess whether they met Diagnostic and Statistical Manual of Mental Disorders (DSM) A criteria for PTSD. RESULTS: In the group of children with cancer, 54% described a cancer-related event as the most stressful event they had experienced. Six distinct categories of cancer-related events and 10 categories of non-cancer-related events were identified. The same noncancer events were identified by children in both groups, and occurred at similar frequencies. The percentage of cancer-related events that met DSM A criteria for PTSD differed dramatically depending on which version of the DSM was applied. CONCLUSIONS: Children do not necessarily view their cancer experience as their most stressful life event. The findings of the current study suggest that the diagnosis of cancer might be better viewed as a manageable stressor rather than a major trauma, and are consistent with the change in the fifth edition of the DSM to eliminate the diagnosis of a life-threatening illness as a qualifying trauma for PTSD. Cancer 2017;123:3385-93. (c) 2017 American Cancer Society.