Background: Next-generation sequencing (NGS) of plasma circulating cell-free DNA (cfDNA) and cfRNA, also known as a “liquid biopsy”, is a minimally invasive technique available in the clinic. Here we report initial liquid biopsy results from stage 3 and 4 solid tumors using the Circulogene Theranostics Personalized Gene Profile (CGP, 50-gene panel) on cfDNA and cfRNA. Methods: DNA mutations detected and, where available, PD-L1 expression, ALK, and ROS1 fusions in RNA were retrospectively compiled from CGP ordered at two centers. To be considered clinically actionable and commercially available (CA), the biomarker had to have demonstrated clinical efficacy in human cancer prospective trials using the biomarker and commercially available drug that can target that biomarker. To be considered a clinical trial possibility (CT), one of the biomarkers was required to have a drug in clinical development using the biomarker for the patient’s cancer type and disease stage listing on clinicaltrials.gov during the time period that CGP was ordered. Results: One hundred forty-five patients (median age 66 years, range 25-95; 35 men and 110 women) underwent CGP testing between November 2015 and October 2017. The majority of cancer types were ovarian, breast, pancreatic, uterine, and prostate. Most common DNA mutations recorded were TP53, PTEN, PI3KCA, SMAD4, and BRAF. There was a median of 2 mutations/patient (range 0-11), with a 0.69% sample failure rate. Overall, 36 cases had no detectable mutations (24.8%). There were six samples with PD-L1 results, and one was positive (16.7%), in the range of expected PD-L1 positivity across solid tumors. In addition to the 36 mutation negative cases, 19 cases had no potential match for CA or CT (e.g. APC, GNAS, SMAD4 mutations). Thus, 89 (61.4%) of cases had the potential for CA and/or CT drug identified by liquid biopsy. CGP is priced at approximately $600 per sample comparable to current reimbursement rate. Conclusions: In this real world experience, despite the low plasma sample input, there was a 0.69% sample failure rate, suggesting CGP in situ enrichment is robust. More experience with this assay and linkage with clinical outcomes is warranted.