Background: ATC is an aggressive disease requiring rapid diagnosis. Targeted therapeutics provide ATC patients (pts) with previously unavailable treatment options. Development of high throughput next generation sequencing (NGS) platforms provides clinicians with the ability to characterize the genomic background of ATC. In ATC, a rapid, blood based test is ideal for several reasons: Lack of available tumor; Expedited results allowing for expanded treatment options; Enhanced enrollment in clinical trials. Methods: We evaluated consecutive ATC pts treated at MD Anderson between 8/2015 and 12/2015. All pts underwent genomic profiling of tumor and cell free circulating DNA (cfDNA, blood based) using NGS. Results: 14 patients were included. The most commonly mutated genes noted on both platforms were BRAF (7/14) and TP53 (11/14). Concordance between tumor and cfDNA data was high for BRAF, PIK3CA, NRAS and moderate for TP53 (Table). Twelve of 14 pts were slated for treatment, one pt elected hospice and another was observed following outside treatment. Seven pts were initiated on targeted therapy or immunotherapy based in part on tumor genomic data. Mean time to results was 13.6 days with blood-based method vs. 16.8 days with tumor-based method. Conclusions: This is one of the largest cohorts of ATC pts who have undergone blood and tumor based genomic profiling. Based on these data, we recommend utilization of both tumor based and cfDNA analysis in order to maximize sensitivity for putative targets. Integration of cfDNA in clinical trials is recommended, as turn-around time is somewhat shorter than that for tissue based testing.