Background: Professional guidelines advise broad molecular profiling for at least 10 biomarkers in Non–Small Cell lung cancer (NSCLC) that have either approved targeted therapies or available clinical trials. Up to 38% of patients with metastatic NSCLC have inadequate tumor samples for comprehensive molecular analysis at diagnosis. Professional guidelines recommend that if there is insufficient tissue to allow for testing of all biomarkers, repeat biopsy and/or plasma testing should be done. While both plasma and tissue testing are currently being incorporated into the standard workup of patients with NSCLC, there is currently no standardized workflow for testing. We performed a retrospective chart review to assess real world liquid and tissue biopsy-based biomarker testing and reflex testing dynamics to understand the current NSCLC biomarker testing scenario in a large US community practice. Methods: Patients with advanced NSCLC (n=250) who received care in a large US community network and were diagnosed or received first-line treatment on or after 1/1/2020 were included in this retrospective observational study. Data was extracted from the electronic medical records in participating practices as well as via abstraction of patient records when available. Patient-level data was anonymized and reported in aggregate. All data collected for this analysis was evaluated in accordance with regulatory requirements and applicable guidance for electronic records. We examined patient demographic information, patient journey, and overall testing for all patients. We also assessed the percentage of liquid and tissue-based testing, test turn-around time (TAT), and timing of first results prior to first-line therapy by test type. Results: 250 patients (128 males [51%] and 115 females [46%]) with stage IV NSCLC. Median age was 71 years (range, 41–90 years). 52 (21%) had never smoked but more than half (143; 57%) were previous smokers; and 227 (91%) had adenocarcinoma. Patients were primarily white (83%) and 77% had an ECOG status of 1 or better. 42% (n=104) of patients received both liquid and tissue testing, while 40% (n=100) received only tissue testing. 16% (n=40) of patients received only liquid testing and 6 patients only had PD-L1 IHC. The median TAT for tissue testing was 11 days and for liquid testing was 7 days. Patients with both a liquid and solid tumor test had results prior to treatment more often (89%) than those who just had a solid (67%) or liquid (72.5%) tumor testing alone. 70 patients received first-line treatment with a targeted therapy based on positive biomarker results. 81% received an EGFR tyrosine kinase inhibitor (TKI), 7% received an ALK TKI, and 5% received a MET inhibitor. Of patients treated, 48.6% (n=34) were treated based on tissue results and 38.5% were treated based on liquid (n=27) results. 12 received liquid only testing and were treated based on liquid biopsy results. Of patients with both liquid and tissue testing (n=30), 15 were treated based on the liquid test results, mainly due to liquid results having faster TAT (n=9) or tissue being insufficient for analysis (TIFA; n=4). Conclusion: In this real-world study, 42% of stage IV NSCLC patients received both liquid and tissue testing. The median TAT for tissue testing was 11 days and for liquid testing was 7 days. Patients with both a liquid and solid tumor test had results in hand prior to treatment more often than those who just had a solid or liquid tumor test. These results demonstrate the effective utilization of tissue and liquid testing in a large US community practice. Strategies to improve time to biomarker test order, enhance percentage of patients tested, and improvement of percentage of patients with test results prior to initiation of therapy are ongoing.