There is limited research around how mental health (MH) student nurses interpret and differentiate between people's religious and cultural beliefs and the existence of psychopathological symptomatology and experiences. Here we focus on one cultural issue that arose from research exploring how MH student nurses approach and interpret religion and culture in their practice - that is, the difficulties in determining the clinical significance of the religious beliefs and experiences expressed by the people they care for. While problems with establishing the cultural boundaries of normality in clinical assessments are an important area of debate in cultural psychiatry, it remains a peripheral issue in MH nurse education. An anthropologically informed qualitative research design underpinned 'critical incident' (CI)-focused ethnographic interviews with 36 second and third-year MH nursing field students and seven undergraduate MH branch lecturers. Follow up focus groups were also carried out. Interview transcripts were subject to thematic analysis. Four subthemes were identified under the broad theme of the clinical significance of religious-type expression and experience: (1) identifying the difference between delusions and religious belief; (2) identifying whether an experience was hallucination or religious experience; (3) the clinical implications of such challenges; and (4) applying religion-specific knowledge. There are clinical implications that may result from the difficulties with assessing the clinical significance of religious beliefs and experiences, identified in both our research and within international cultural psychiatry literature and research. Misinterpretation and therefore wrongly assessing someone's experience as pathological is a significant concern. It is suggested that CI analysis could be adapted to help nurses, nursing students and nurse educators recognize the religious dimensions of mental distress, particularly those that then potentially impact upon the accuracy and person centeredness of clinical assessment. Further research is proposed to investigate the clinical assessment and training needs of nurses in the area of religion and mental distress.