Background: Consensus guidelines strongly recommend urine drug screening (UDS) for all patients receiving opioids for cancer pain management. However, implementation of UDS in oncology clinics is underreported. The primary aim of this study was to evaluate incidence of unexpected UDS results among patients with lung cancer after implementation of confirmatory UDS in a thoracic oncology clinic. Methods: This is a single-institution retrospective study of UDS results among patients diagnosed with any stage thoracic malignancy before and after expansion of chromatography-based UDS facilitated by a palliative care provider embedded in a thoracic medical oncology clinic. Patients were included if their first UDS was collected during the year prior to (pre-intervention) or during the 12 months after (post-intervention) opening of the embedded Thoracic Onco-Palliative Clinic on September 5, 2018. In the pre-intervention period, UDS was routinely ordered for only patients referred to a standalone palliative care clinic. This 2-step UDS includes immunoassay and chromatography-based testing followed by interpretation of results by a specialty-trained palliative care clinical pharmacist. In the post-intervention period, UDS was expanded to include any patient seen by Thoracic Medical Oncology regardless of palliative care referral status. A Kaplan-Meier curve and log-rank test were used to compare time to first unexpected UDS between cohorts. Results: More patients had UDS testing in the post-intervention (n = 182) versus pre-intervention (n = 61) period. A higher volume and proportion of patients had unexpected UDS results in the post-cohort (25/182; 13.7%) compared to pre-cohort (6/61; 9.8%), although this difference was not statistically significant (p = 0.43). The number of UDS tests per patient was significantly higher (p < 0.01) in the post-cohort (mean (SD): 2.4 (2.7)) vs. pre-cohort (1.5 (1.3)). A larger proportion of pre-cohort patients completed only one UDS during the study period (pre: 73.8% (45/61); post: 53.3% (97/182); p < 0.01). In the post-cohort, 58 (31.9%) patients completed UDS ordered by oncology team prior to palliative care referral compared to 0 patients in the pre-cohort; 29 (21.4%) patients completed UDS without receiving outpatient palliative care compared to 0 patients in the pre-cohort. Kaplan-Meier curves for the pre- and post-cohorts were similar during the first 6 months of drug screening (p = 0.7) and diverged after 6 months, with a higher probability of detecting an unexplained UDS in the post cohort at 24 months (Pre: 15.0%; Post: 40.0%). Conclusions: Implementation of confirmatory UDS in a thoracic oncology clinic facilitates closer monitoring for nonprescribed substance use during opioid management and continued detection of unexpected UDS results up to 24 months.