Objective The health status and psychosocial well‐being of multiple primary cancer (MPC) survivors are under‐researched. Methods In total, 3615 survivors identified from the Eindhoven Cancer Registry between 2008 and 2009 were assessed. About one in six survivors had survived MPC (n = 556). All survivors completed questionnaires on health status (SF‐36/European Organization of Research and Treatment of Cancer quality of life module), mental health (Hospital Anxiety and Depression Scale) and impact of cancer (Impact of Cancer). Results Compared with single primary cancer survivors, MPC survivors reported significantly poorer scores on general health and higher symptom scores on diarrhoea and fatigue. Significantly more MPC survivors met the subclinical cut‐off score of ≥8 points on the Hospital Anxiety and Depression Scale depression subscale (27% vs. 19%, p = 0.0001). MPC survivors also reported significantly greater negative impact of cancer (namely body changes and life interferences) and positive impact of health awareness on their lives. All results were adjusted for age at survey, time since last diagnosis, sex, comorbidity, body mass index and marital status. In secondary analyses, MPC survivors with different primary cancer combinations or time interval between primary cancer diagnoses had comparable health status and psychosocial well‐being. Conclusion Multiple primary cancer survivors reported a poorer health status and, in general, experienced a greater negative impact of cancer on their psychosocial well‐being than single primary cancer survivors. Copyright © 2012 John Wiley & Sons, Ltd.