This longitudinal waitlist-controlled study evaluated the effects of Mindfulness-Based Stress Reduction (MBSR) on spirituality, posttraumatic growth (PTG), and mindfulness in cancer patients. The study also assessed whether increased mindfulness mediated the effects of MBSR on spirituality and PTG. Patients were either registered for immediate participation in MBSR (n=135), or were naturally waiting for the next program (n=76). Participants completed questionnaires pre-, mid-, and post-MBSR, or waiting period. Hierarchical linear modeling (HLM) was employed to assess changes over time as a function of condition (MBSR vs. waitlist). Mediation was tested using linear regression and bootstrapping. MBSR participants demonstrated increased spirituality, PTG, and mindfulness, relative to controls. Change in all mindfulness facets mediated the effect of MBSR on spirituality and PTG. The development of mindfulness skills through MBSR may facilitate a sense of meaning, peacefulness, connectedness, and personal growth in cancer patients. This investigation contributes to an emerging focus on determining ‘how’ mindfulness-based interventions work.