The present study evaluates the influence of spirituality/religiosity (S/R) on the coping strategies used by people with cancer (breast and prostate) compared with those without cancer, in a sample of 445 Spanish participants (160 with cancer and 285 without). Significant interactions between the presence of cancer and S/R are observed in the use of coping strategies such as religion, humor and disconnection. Spirituality as a predictor variable through the use of religion as a strategy, increased the explanatory capacity of age by 58.9% (β = .794) while praying/talking to God predicts the use of this strategy with a β = .383. In people with cancer, active coping was predicted by spirituality (β = .327). However, spirituality was a negative predictor of maladaptive coping, with a beta coefficient equal to .383. The data suggest that patients' beliefs need to be considered by health care professionals when designing interventions.