Measures of spirituality often contain the dimension existential well-being (EWB). However, EWB has been found to overlap with emotional and psychological well-being. Using the Spiritual Attitude and Involvement List (SAIL), we have further investigated the overlap between aspects of spirituality and of well-being among patients with cancer, by determining a) the divergent validity of the subscales of the SAIL compared with a well-being questionnaire and b) the differences in their associations to changes in pain and fatigue, and the occurrence of negative life events. Our findings suggest that a sense of trust that one is able to cope with difficulties of life belongs to the realm of well-being, instead of spirituality. Other aspects, such as a sense of meaning in life, seem more similar to spirituality than to well-being. These results can bring researchers a step further toward constructing “pure” spirituality and well-being measures, which will allow them to investigate the (causal) relationship between these constructs.