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Religiosity/spirituality is linked to better well-being. Spiritual Framework of Coping (SFC) model proposes paths to achieving emotional well-being, through spiritual connections/coping and meaning-making. To test SFC, four models were examined in 103 cancer patients, assessed at diagnosis, and again 12-/18-/24-/36- months post-diagnosis. Measures include religious and active-cognitive coping, religious attendance/importance, positive affect, spiritual meaning, and psychological distress (mood and depressive symptoms). Mediation was established by hierarchical multiple regressions and a Sobel test statistic. Positive affect served as a mediator between positive coping and spiritual meaning, and between spiritual connections and spiritual meaning. Spiritual meaning served as a mediator between positive affect and distress. Results support the SFC model, highlighting the importance of meaning and positive affect in adjusting to cancer. Coping, Meaning, Distress