BACKGROUND: Although mindfulness-based interventions have been widely examined in patients with nonmetastatic cancer, the feasibility and efficacy of these types of programs are largely unknown for those with advanced disease. We pilot-tested a couple-based meditation (CBM) relative to a supportive-expressive (SE) and a usual care (UC) arm targeting psychospiritual distress in patients with metastatic lung cancer and their spousal caregivers. PATIENTS AND METHODS: Seventy-five patient-caregiver dyads completed baseline self-report measures and were then randomized to one of the three arms. Couples in the CBM and SE groups attended four 60-minute sessions that were delivered via videoconference. All dyads were reassessed 1 and 3 months later. RESULTS: A priori feasibility benchmarks were met. Although attendance was high in both groups, dyads in the CBM group indicated greater benefit of the sessions than those in the SE group (patients, CBM mean = 2.63, SE mean = 2.20, p = .003; spouses, CBM mean = 2.71, SE mean = 2.00, p = .005). Compared with the UC group, patients in the CBM group reported significantly lower depressive symptoms (p = .05; d = 0.53) and marginally reduced cancer-related stress (p = .07; d = 0.68). Medium effect sizes in favor of the CBM compared with the SE group for depressive symptoms (d = 0.59) and cancer-related stress (d = 0.54) were found. Spouses in the CBM group reported significantly lower depressive symptoms (p < .01; d = 0.74) compared with those in the UC group. CONCLUSION: It seems feasible and possibly efficacious to deliver dyadic interventions via videoconference to couples coping with metastatic lung cancer. Mindfulness-based interventions may be of value to managing psychological symptoms in the palliative care setting. Clinical trial identification number. NCT02596490 IMPLICATIONS FOR PRACTICE: The current randomized controlled trial has established that a mindfulness approach to the management of patients' and spouses' psychospiritual concerns is acceptable and subjectively deemed more beneficial than a supportive-expressive treatment for patients with metastatic non-small cell lung cancer (NSCLC). We also revealed that videoconference delivery, here FaceTime, is an acceptable approach even for geriatric patients with metastatic NSCLC and that patients and their spousal caregivers prefer a dyadic delivery of this type of supportive care strategy. Lastly, this trial has laid the foundation for the role of mindfulness-based interventions in the palliative care setting supporting patients with advanced NSCLC and their spousal caregivers.