Higher levels of religious and spiritual engagement have been shown to be associated with better adjustment in dealing with serious illness. Nevertheless, the pattern of such engagement may vary substantially among individuals. This paper presents exploratory research with the goal of identifying subgroups of individuals with non-terminal cancer who vary along multiple dimensions of religious/spiritual (R/S) involvement and well-being. Cluster analysis utilized both R/S (FACIT-Sp) and quality of life variables (e.g., FACT-G) to identify subgroups within 114 individuals (Median age = 65; 59% female) under care for cancer. Additional R/S and adjustment variables were used to explore further distinctions among these groups. Four clusters were identified: High R/S (45%), with the lowest depression; Low R /High S (25%), also with good adjustment; Negative Religious Copers (14%), with the highest depression; and Low R/S (16%), with the poorest adjustment to cancer. The results support the value of differentiating patterns of religious and spiritual engagement in relation to well-being, with implications for matching psycho-social interventions with individuals.