BACKGROUND: This study sought to inductively derive core themes of religion and/or spirituality (R/S) active in patients’ experiences of advanced cancer to inform the development of spiritual care interventions in the terminally ill cancer setting. METHODS: This is a multisite, cross-sectional, mixed-methods study of randomly-selected patients with advanced cancer (n = 68). Scripted interviews assessed the role of R/S and R/S concerns encountered in the advanced cancer experience. Qualitative and quantitative data were analyzed. Theme extraction was performed with interdisciplinary input (sociology of religion, medicine, theology), utilizing grounded theory. Spearman correlations determined the degree of association between R/S themes. Predictors of R/S concerns were assessed using linear regression and analysis of variance. RESULTS: Most participants (n = 53, 78%) stated that R/S had been important to the cancer experience. In descriptions of how R/S was related to the cancer experience, five primary R/S themes emerged: coping, practices, beliefs, transformation, and community. Most interviews (75%) contained two or more R/S themes, with 45% mentioning three or more R/S themes. Multiple significant subtheme interrelationships were noted between the primary R/S themes. Most participants (85%) identified 1 or more R/S concerns, with types of R/S concerns spanning the five R/S themes. Younger, more religious, and more spiritual patients identified R/S concerns more frequently (beta = -0.11, p < 0.001; beta = 0.83, p = 0.03; and beta = 0.89, p = 0.04, respectively). CONCLUSIONS: R/S plays a variety of important and inter-related roles for most advanced cancer patients. Future research is needed to determine how spiritual care can incorporate these five themes and address R/S concerns.