Acceptance of cancer has long been recognized as playing a critical role in psychological adjustment to the illness, but its associations with distress outcomes have not been quantitatively reviewed. Informed by coping theory and third wave conceptualizations of acceptance, we first propose an integrated model of acceptance of cancer. Then we examine the strength of the relationships between acceptance of cancer and general and cancer-specific distress in cancer patients and potential moderators of these relationships. CINAHL, Embase, MEDLINE, PsycINFO, PsycARTICLES, and Web of Science databases were searched. Random-effects meta-analyses were conducted on 78 records (N = 15,448). Small-to-moderate, negative, and significant relationships were found between acceptance of cancer and general distress (r = -0.31; 95% CI: -0.36 to -0.26, k = 75); cancer-specific distress (r = -0.18; 95% CI: -0.21 to -0.14, k = 13); depressive symptoms (r = -0.25; 95% CI: -0.31 to -0.19, k = 41); and anxiety symptoms (r = -0.22; 95% CI: -0.30 to -0.15, k = 29). Age, marital status, and stage of cancer were identified as significant moderators. Findings suggest that acceptance of cancer may be important to target in interventions to reduce general and cancer-specific distress in cancer patients. Future research should focus on developing multifaceted measures of acceptance and identifying theory-based psychological and social processes that lead to greater acceptance.