Purpose Large cohort studies are needed taking into account cancer-related, personal, biological, psychobehavioral, and lifestyle-related factors, to guide future research to improve treatment and supportive care. We aimed to evaluate the feasibility of a comprehensive baseline assessment of a cohort study evaluating the course of quality of life (QoL). Methods newly diagnosed head and neck cancer (HNC) patients were asked to participate. Assessments consisted of questionnaires (635 items), a home visit (including a psychiatric interview, physical tests, and blood and saliva collection), and tissue collection. Representativeness of the study sample was evaluated by comparing demographics, clinical factors, depression, anxiety, and QoL between responders and nonresponders. Feasibility was evaluated covering the number of questions, time investment, intimacy, and physical burden. Results During the inclusion period (4 months), 15 out of 26 (60%) patients agreed to participate. Less women participated, 13%in responders group versus 63%in non-responders group (p=0.008). No other differences were found between responders and non-responders. Responders completed more than 95% of the questionnaires’ items and rated the number of questions, time investment and intimacy as feasible, and the physical and psychological burden as low. It took on average 3 h to complete the questionnaires and 1.5 h for the home visit. Conclusions This study reveals that a comprehensive assessment including various questionnaires, physical measurements, and biological assessments is feasible according to patients with newly diagnosed HNC. A large prospective cohort study has started aiming to include 739 HNC patients and their informal caregivers in the Netherlands.