Older people with cancer often face the prospect of cognitive and physical frailty, increased vulnerability of psychological distress and limited access to resources. These factors present ethical and methodological challenges for conducting research in such patients, especially interviews in acute care settings. This paper discusses these challenges using experiences from an ongoing research project. The project is a patient-focused study on the perceptions of older people with cancer regarding information provided to them, decision making and treatment. Interviews with patients aged 65 or over with a cancer diagnosis are conducted in two clinical settings, care of the elderly wards and a cancer centre whilst they are in-patients. Patients' cognitive and physical status are assessed using clinical measures, whereas socio-demographic and medical data are obtained from patient files. Ethical challenges, including procedures to obtain valid consent, as well as methodological choices, including recruitment procedures and patient conditions are presented and debated with reference to previous literature. Suggestions for future research with older people with cancer are made based both on current experience and previous literature.