Background Medical illnesses are major stressors not only for the patients but also for their family caregivers, yet existing tools are inadequate to assess mechanistic response patterns to such stressors.Purpose We sought to validate a stress induction task that pertains to close relationships and health-related concerns with adult patients with cancer and their family caregivers.Methods Patients newly diagnosed with colorectal cancer (n = 123, 56 years old, 34% female, 60% Hispanic, 6.5 months post-diagnosis) and their family caregivers (55 years old, 66% female, 59% Hispanic) underwent an experimental session during which both individuals imagined a scenario where one person is hit by a car (patient) and the partner (caregiver) has no means to provide or seek out help for the victim. The session consisted of 6 phases: baseline, scenario provision, speech preparation, speech by caregiver, speech by patient, and recovery.Results Results of general linear modeling with repeated measures revealed that the task induced significant affective, stress, and cardiovascular responses in both patients and caregivers. Stress reactivity and recovery patterns, however, varied by patients versus caregivers, stress induction phases, and the types of assessment.Conclusions Findings suggest the newly developed stress task as an acceptable tool for studying stress regulation in medical and family contexts. With further validation, this tool may help identify psychological and physiological pathways to improve the stress coping outcomes of adult patients with cancer and their family caregivers. Medical illnesses are major stressors not only for the patients but also for their family caregivers. However, existing tools are inadequate to assess mechanistic response patterns to such stressors. Thus, we sought to validate a stress induction task that pertains to close relationships and health-related concerns with adult patients with cancer and their family caregivers. Patients diagnosed with colorectal cancer (n = 123, 56 years old, 34% female, 60% Hispanic, 6.5 months post-diagnosis) and their family caregivers (55 years old, 66% female, 59% Hispanic) underwent an experimental session during which both individuals imagined a scenario where one person is hit by a car (patient) and the partner (caregiver) has no means to provide or seek out help for the victim. Results revealed that the task induced significant affective, stress, and cardiovascular responses in both patients and caregivers. Stress reactivity and recovery patterns, however, varied by patients versus caregivers, stress induction phases, and the types of assessment. Findings suggest the newly developed stress task as an acceptable tool for studying stress regulation in medical and family contexts. With further validation, this tool may help identify psychological and physiological pathways to improve the stress coping outcomes of adult patients with cancer and their family caregivers.