Background: Next generation sequencing (NGS)-based panels are routinely used in the diagnosis of mNSCLC, guidelines recommending assessing 12 genes for small variants (SV), (EGFR, BRAF, KRAS, MET, ERBB2); fusions (F), (ALK, ROS1, RET, NTRK1, NTRK2, NTRK3); and copy number variants (CNV), (MET) to assess eligibility for targeted drug therapies. Reimbursement is often limited to targeted panels; yet, a comprehensive review of targeted panels’ ability to capture all recommended biomarkers has not been reported. Methods: Targeted panels were classified as ≤50 and 51-100 genes. We searched the DEX Diagnostics Exchange Registry for NGS-based lung cancer and solid tumor targeted panels. Each panel was compared against the 12 recommended genetic variants. If the type of genetic analysis (SV/F/CNV) was unclear, labs were contacted for clarification. Fusion assays by PCR or FISH with reflex testing to NGS were included. Results: 30 targeted NGS panels from 21 commercial labs were identified; 13 (43%) were specific to lung cancer. Six of 13 panels assessing fusions used FISH or PCR not NGS alone. 12 panels reported only SV, 8 small SV/F, 5 SV/CNS, and 5 all three variant types. Only 1 of the 30 panels (51-100 genes) captured all 12 biomarkers with correct variant types. Of 20 panels reporting ALK, RET, and ROS1, only 11(55%) reported fusions. Of the 5 reporting all three variant types, NTRK fusions were most commonly absent. On average, solid tumor panels sequenced twice as many genes (51 vs. 24) but were no more likely to capture all recommended biomarkers ((1/17 (6%) vs. 0/13 (0%), (p>0.05)). The average biomarkers captured in lung vs. solid tumor panels were 7.9 and 6.6, respectively (p>0.05), while in ≤50 gene panels vs. 51-100 gene panels, 7.0 and 7.6, respectively (p>0.05). Conclusions: Of 30 commercially available NGS panels with <100 genes, only one captured all recommended gene variant types for mNSCLC. Failure to capture all biomarkers was independent of panel size or specificity to lung cancer. NGS panels including small variants, fusions, and copy number variants assessed more biomarkers. Medical oncologists and clinical pathologists ordering targeted NGS panels for the management of patients with mNSCLC must ensure they assess all biomarkers relevant to targeted therapies. Insurers reimbursing targeted panels should acknowledge the inadequacy of <100 gene panels alone to provide guideline-concordant molecular diagnostic testing.