Background and aims: there are few certainties on the psychological features of patients with cancer. The aim of the present study is to evaluate differences in Psychological Well-being (PWB), Psychological Flexibility (PF), and Anxiety between patients with cancer and general population control subjects, and to test a model in which PF mediates the relation between PWB and Anxiety in both groups. Methods: participants were recruited in the Onchology Units of the University of Pisa, Italy, and among relatives of students attending courses at the Medical School of the same University. Measures of PWB (Psychological Well Being Scale), PF (Acceptance and Action Questionnaire II), and Anxiety (Hospital Anxiety and Depression Scale) were obtained from standardised, self-administered questionnaires. Statistical analyses focused on between-groups differences (ANCOVA) and on correlations among the major variables under study. Regression analyses were performed to test the mediational model. Results: there were no differences between patients with cancer and control subjects in PWB, PF and Anxiety levels. In both groups, PWB significantly predicted PF and Anxiety, and PF in turn predicted Anxiety. The effect of PWB on Anxiety was not significant anymore when controlling for PF scores, whereas the latter still predicted them. Conclusions: inconsistent with most psychological models on well-being, but consistent with the hypothesis of the study, there were no differences between the two groups in PWB and PF. PF mediated the relation of PWB with Anxiety either in cancer patients and in the control group.