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Research biopsies are an increasingly important component of clinical trials, but there are concerns that biopsies may deter patients from participating in research.Patients participating in a single-center study investigating the feasibility of molecular profiling in advanced gastrointestinal cancers were asked to complete a questionnaire regarding their reasons for consenting/declining optional research biopsies and blood samples. These samples were mainly for exploratory translational research and were unlikely to influence patients' treatment.One hundred ninety-six (88%) of the 222 patients registered in the study completed the questionnaire. One hundred twenty-six patients (64%) stated they consented to a biopsy and 180 patients (92%) to blood sample collection. Male patients (P = .033) and patients with a good performance status (PS) were more willing to consent to a biopsy (79% for PS 0, 63% for PS 1, 43% for PS 2; P = .012). Eighty-eight patients (70%) who consented to a biopsy gave an altruistic reason (eg, to help research and/or others) as a reason why they consented. Only 8 patients (6%) consented solely because they believed it might influence their treatment. Reasons for declining biopsies included a wish to avoid additional procedures (n = 18; 29%) and previous unpleasant biopsy experiences (n = 9; 15%).Many patients with advanced gastrointestinal cancer appear willing to undergo biopsies for exploratory research purposes. In our study, patients who consented to a biopsy mainly did so for altruistic reasons and/or a wish to contribute to scientific research.Little is known about patients' attitudes toward research biopsies. A total of 222 patients with advanced gastrointestinal cancers in a molecular profiling study were asked to complete a questionnaire about their reasons for consenting/declining optional research biopsies. Many patients were willing to undergo research biopsies and were frequently motivated by altruistic reasons and/or a wish to contribute to scientific research.