The authors evaluated mechanisms of change for a coping and communication-enhancing intervention (CCI) and supportive counseling (SC). They proposed that the effects of CCI on depressive symptoms would be mediated by psychological processes targeted by CCI, namely increases in the following: positive reappraisal, acceptance, planful problem solving, attempts to understand emotional reactions to cancer, emotional expression, seeking of emotional and instrumental support, and self-esteem. The authors hypothesized that the effects of SC on depressive symptoms would be mediated by the processes encouraged by SC, in this case increases in the following: expression of emotions, attempts to understand emotional reactions to cancer, and self-esteem. Three hundred fifty-three women were randomized to a CCI, SC, or usual care control group and completed measures at preintervention and 3, 6, and 9 months later. The effects of CCI were fully mediated by positive reappraisal, problem solving, and self-esteem and partially mediated by emotional expression. The effects of SC were partially mediated by positive reappraisal. These findings provide support for hypothesized mediators for CCI. The authors were less able to identify mediators for SC. Future research might benefit from identifying SC mediators.