ABSTRACT: To determine the effectiveness of the Alleviating Depression Among Patients With Cancer (ADAPt-C) collaborative care management for major depression or dysthymia.Study patients included 472 low-income, predominantly female Hispanic patients with cancer age >or= 18 years with major depression (49%), dysthymia (5%), or both (46%). Patients were randomly assigned to intervention (n = 242) or enhanced usual care (EUC; n = 230). Intervention patients had access for up to 12 months to a depression clinical specialist (supervised by a psychiatrist) who offered education, structured psychotherapy, and maintenance/relapse prevention support. The psychiatrist prescribed antidepressant medications for patients preferring or assessed to require medication.At 12 months, 63% of intervention patients had a 50% or greater reduction in depressive symptoms from baseline as assessed by the Patient Health Questionnaire-9 (PHQ-9) depression scale compared with 50% of EUC patients (odds ratio [OR] = 1.98; 95% CI, 1.16 to 3.38; P = .01). Improvement was also found for 5-point decrease in PHQ-9 score among 72.2% of intervention patients compared with 59.7% of EUC patients (OR = 1.99; 95% CI, 1.14 to 3.50; P = .02). Intervention patients also experienced greater rates of depression treatment (72.3% v 10.4% of EUC patients; P < .0001) and significantly better quality-of-life outcomes, including social/family (adjusted mean difference between groups, 2.7; 95% CI, 1.22 to 4.17; P < .001), emotional (adjusted mean difference, 1.29; 95% CI, 0.26 to 2.22; P = .01), functional (adjusted mean difference, 1.34; 95% CI, 0.08 to 2.59; P = .04), and physical well-being (adjusted mean difference, 2.79; 95% CI, 0.49 to 5.1; P = .02).ADAPt-C collaborative care is feasible and results in significant reduction in depressive symptoms, improvement in quality of life, and lower pain levels compared with EUC for patients with depressive disorders in a low-income, predominantly Hispanic population in public sector oncology clinics.