Objective: In the last decade, some attention has been given to spirituality and faith and their role in cancer patients' coping. Few data are available about spirituality among cancer patients in Southern European countries, which have a big tradition of spirituality, namely, the Catholic religion. As part of a more general investigation (Southern European Psycho-Oncology Study -SEPOS), the aim of this study was to examine the effect of spirituality in molding psychosocial implications in Southern European cancer patients.Method: A convenience sample of 323 outpatients with a diagnosis of cancer between 6 to 18 months, a good performance status (Karnofsky Performance Status . 80), and no cognitive deficits or central nervous system (CNS) involvement by disease were approached in university and affiliated cancer centers in Italy, Spain, Portugal, and Switzerland (Italian speaking area). Each patient was evaluated for spirituality (Visual Analog Scale 0-10), psychological morbidity (Hospital Anxiety and Depression Scale-HADS), coping strategies (Mini-Mental Adjustment to Cancer -Mini-MAC) and concerns about illness (Cancer Worries Inventory -CWI).Results. The majority of patients (79.3%) referred to being supported by their spirituality/ faith throughout their illness. Significant differences were found between the spirituality and non-spirituality groups ( p 0.01) in terms of education, coping styles, and psychological morbidity. Spirituality was significantly correlated with fighting spirit (r ¼ 20.27), fatalism (r ¼ 0.50), and avoidance (r ¼ 0.23) coping styles and negatively correlated with education (r ¼ 20.25), depression (r ¼ 20.22) and HAD total (r ¼ 20.17).Significance of results: Spirituality is frequent among Southern European cancer patients with lower education and seems to play some protective role towards psychological morbidity, specifically depression. Further studies should examine this trend in Southern European cancer patients.