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The aim of this study was to determine the prevalence, modalities, and determinants of use of unconventional therapies among children with cancer receiving conventional treatment at an urban academic medical center in the United States.We interviewed the parents of patients and/or patients who were receiving or had received conventional therapy for treatment of childhood cancer. Of 78 patients/parents asked, 75 consented to the interview, which included demographic factors, life events, and use of unconventional therapies. All participants also consented to the abstraction of chart data for this study.Overall, 84% of respondents reported the use of one or more unconventional therapies. The most commonly used modalities were changes in diet, nutritional and herbal agents, and mind/body treatments. Most users had tried more than one unconventional modality. No difference in use was seen by cancer diagnosis, race/ethnicity, socio-economic status, or educational attainment of the respondent. Of the therapies used, 50% were not reported to the physicians. Of patients reporting use of an unconventional approach, 85% were concurrently enrolled on clinical trials for primary treatment of their cancer.The use of unconventional therapies is highly prevalent among children with cancer and is not associated with demographic or clinical factors or participation in clinical trials. The possibility that an unconventional treatment may interact with a protocol treatment underscores the need for more information about the use of such therapies among all patients.