Problem: Approximately 50% of cancer patients experience clinically significant cancer-related distress. Unmanaged distress has been linked to decreased medication adherence, increased visits to the emergency room and oncology clinic, increased hospital stays, decreased quality of life and decreased overall survival. At a university-based cancer center in the mid-Atlantic region, informal assessment of patient distress was provider dependent and as a result was inconsistently conducted and documented. Purpose: The purpose of this quality improvement (QI) project was to implement a systematic screening protocol for distress which included a screening tool, staff training, as well as referral processes to identify and manage distress in adult patients with metastatic colorectal cancer. Methods: The National Comprehensive Cancer Network (NCCN) Distress Thermometer and Problem List (DT&PL) was integrated into the patient portal as a questionnaire and sent to patients with metastatic colorectal cancer prior to treatment to be completed prior to their infusion appointment. Infusion nurses reviewed the distress screening with patients during their appointment and made appropriate referrals to clinic-embedded resources such as social work, psychiatry, pain and palliative care, and/or pastoral care based on questionnaire results. Results: The NCCN DT&PL was successfully integrated into the portal as a questionnaire. Overall, 64% of patients completed the questionnaire at least once and 39% of the completed screens indicated high distress. All patients who indicated high distress had documented nursing interventions and/or referrals. Conclusions: Evidence-based distress screening and referral is a feasible practice change to improve patient outcomes. Key facilitators were integration into the electronic health record and personnel to support to initiative.