This study examined the potential role of social support, neuroticism, and self-efficacy as predictors of the short-term and long-term adaptation to the diagnosis of cancer. Psychological adjustment was defined in terms of psychological distress. It is argued that these factors may provide insights that might be helpful in the provision of medical care to patients. We hypothesized that they would be especially predictive of long-term psychological adjustment. The study was conducted in a truly prospective design with one pre-morbid assessment and two post-morbid assessments used in the present analyses. Participants of a baseline assessment among 5279 subjects (aged 57 years and older) in 1993 were monitored for cancer incidence by their general practitioners. The study sample included 99 cancer patients who had completed all pre-morbid and post-morbid assessments. Multivariate analyses revealed that high neuroticism was associated with higher levels of distress in the short- and long-term. Higher levels of social support were associated with higher levels of distress in the long-term. The direction of this association was opposite to what might be expected on the basis of the literature. Implications of the findings for health care as well as explanations for the social support findings are discussed.