Psychological distress, such as ongoing depression and anxiety-related symptomatology, has been associated with a higher risk of incident cancer and poorer survival, although previous studies have not compared prognostic and etiological effects within the same sample. We examined the association between psychological distress and cancer mortality in a sample comprising participants with and without previous cancer admissions.Data were collected from a community-based sample of 15,453 men and women (including 295 people with cancer history) and prospectively linked to a patient-based database of cancer registry and deaths during an average follow-up of 7.0+/-3.3 years. Psychological distress was assessed using the 12-item version of the General Health Questionnaire (GHQ-12).There were 425 incident cancer deaths. Psychological distress (GHQ-12 > or =4) was associated with increased cancer mortality in participants with cancer history [age, gender, social status, marital status, body mass index, smoking, alcohol, and physical activity; adjusted hazard ratio (HR)=1.97; 95% confidence interval (95% CI)=1.05-3.71; P=.035], but not in participants without cancer history. Among participants without cancer history, there was, however, an association between distress and lung cancer death (age- and gender-adjusted HR=2.04; 95% CI=1.36-3.06; P=.001), although adjustment for covariates attenuated this association.Psychological distress was a predictor of cancer mortality, especially in lung cancer. The presence of participants with cancer history in community-based cohorts may overestimate the association between psychological distress and subsequent cancer mortality.