Background: Testicular germ cell tumors (GCT) infrequently harbor somatic mutations. ctDNA assessment allows the noninvasive genomic profiling of malignancies and may assist with understanding molecular evolution of resistance. We report ctDNA profiling of patients (pts) with testicular GCTs. Methods: 40 patients (pts) with advanced testicular GCTs from multiple institutions in the USA that underwent ctDNA analysis using the Guardant (G)-360 platform were eligible and a total of 48 samples were collected. 36 pts had one sample, 3 pts had 2 samples, 1 pt had 6 samples. De-identified demographic data were collected in addition to data for ctDNA alterations. G360 employed a CLIA-certified ctDNA panel that assessed single nucleotide variant and copy number alterations in 68 to 73 genes for potentially actionable genomic alterations. Variants reported at least 3 times in the Catalogue of Somatic Mutations in Cancer (COSMIC) database or found in OncoKB were considered pathogenic. Results: Of 40 patients with testicular GCTs, 13pts (33%) were post systemic therapy. The median age was 36 years (range 20-61). 199 ctDNA alterations were detected in 35 patients (87.5%) across 41 genes. Among the 199 alterations, 102 were believed to be pathogenic and detectable in 26 samples from 25 pts (62.5) (%). The most common pathogenic somatic alterations were KRAS (n = 16/102, 16%), TP53 (n = 16/102, 16%), CCND2 (n = 9/102, 9%), CDK6 (n = 9/102, 9%), MET (n = 9/102, 9%), and RAF1 (n = 6/102, 6%). Conclusions: ctDNA alterations were frequently detected in resistant testicular GCTs and appear similar to alterations previously described in tumor tissue analyses of testicular GCTs. Given that ctDNA offers a non-invasive means of profiling tumor DNA, further development of this promising modality is warranted to study the evolution of resistance to cisplatin-based chemotherapy and new potentially actionable alterations.