To investigate the role of psychosocial variables and psychological vulnerability on adjustment to cancer, a study was undertaken on 157 cancer patients. Assessment of adjustment to cancer (Mental Adjustment to Cancer-MAC-scale), social support (Social Support Index), external locus of control (ELC scale), psychiatric history and present mental status (DSM-III- R) was carried out. The results indicated that the MAC dimension Fighting Spirit (FS) was related to low ELC and high social support, while an opposite association was shown for Helplessness (H) and Fatalism (F). According to MAC cut-off scores, ‘cases’ reported higher ELC and lower social support than ‘non-cases’. Patients with a lifetime history of emotional disorders, as well as a present DSM-III-R diagnosis, showed a style of mental maladjustment to cancer (low FS, high H, F and Anxious Preoccupation). The findings seem to confirm the utility of using the MAC in oncologic settings and the importance of prior psychological problems, present emotional disorders, external locus of control and inadequate interpersonal support in favouring less effective strategies of adjustment to cancer.