Abstract Purpose: OncoBEAM™ is a circulating tumor DNA (ctDNA) test that uses the BEAMing digital PCR technology. We clarified the association between the baseline tumor burden and discordance in the RAS status by metastatic sites in patients with a single metastatic site. Experimental Design: Data from previous Spanish and Japanese studies investigating the concordance of the RAS status between OncoBEAM™ and tissue biopsy in 221 patients with metastatic colorectal cancer (mCRC) were used. We collected data from patients with liver, peritoneal, or lung metastases and evaluated the concordance rates according to the metastatic site and the association between the concordance rate and tumor burden. Results: Patients had metastases in the liver (n = 151), peritoneum (n = 25), or lung (n = 45) with concordance rates of 91% (95% confidence interval, 85%–95%), 88% (68%–97%), and 64% (49%–78%), respectively. Factors associated with concordance included the baseline longest diameter and lesion number (P = 0.004), and sample collection interval (P = 0.036). Concordance rates ≥90% were observed in the following groups: liver metastases alone, regardless of the baseline longest diameter and lesion number; peritoneal metastases alone in patients with a baseline longest diameter ≥20 mm; and lung metastases alone in patients with a baseline longest diameter ≥20 mm and/or number of lesions ≥10. Conclusions: Plasma ctDNA-based liquid biopsy in patients with mCRC may be useful depending on the metastatic site. The maximum diameter and lesion number should be carefully considered when determining patients' RAS status with only peritoneal or lung metastases.