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Use of comprehensive genomic profiling (CGP) in metastatic colorectal cancer (mCRC) is limited. We estimated impacts of expanded 1 L CGP, using the Tempus xT test, on detection of actionable alterations and testing budgets in a modeled US health plan over two-years. A decision analytic model was developed to estimate the impact of replacing 20% of usual testing (a mix of CGP and non-CGP) with Tempus xT CGP. Actionable alterations for matched treatments or clinical trial included KRAS, NRAS, RAF, BRAF, deficient mismatch repair (dMMR)/microsatellite instability (MSI), NTRK, RET, EGFR, HER2, MET, PIK3CA and POLE1. Costs included initial and repeat testing, physician-associated and administrative costs. In a hypothetical five-million-member plan, 50% Medicare and 50% commercial, 1,112 new cases of mCRC were expected per year. Of these, 566 (51%) would undergo 1 L molecular testing, with 55 re-tested upon progression. Based on current testing rates, there were an expected 521 missed opportunities for genomically informed treatment (47% of new cases), with 442 missed due to lack of testing and 79 due to testing without CGP. Replacing 20% of usual testing with Tempus xT CGP was associated with up to a $0.003 per member per month testing cost increase (net total cost of $202,102 for the five-million-member plan) and 15.5 additional patients with an opportunity for genomically informed care (12.7 patients for treatment and 2.8 for clinical trial). The testing total cost (initial test, repeat test, biopsy and physician services, and administrative cost) to put one additional patient with mCRC on matched therapy or matched clinical trial was estimated to be $13,005. Number needed to test to identify one actionable alteration with Tempus xT CGP versus usual testing was 7.8 patients. Conservative assumptions were made for inputs with limited evidence. Based on high concordance rates with dMMR/MSI status, tumor mutational burden (TMB) status was not calculated separately. Replacing 20% of usual testing with Tempus xT CGP was associated with a small incremental testing cost and can identify meaningfully more actionable alterations.