Molecular profiling has become essential for the treatment of metastatic colorectal cancer (CRC) when surgery cannot be considered and systemic therapy is recommended. CRC has several potential mutations that are diagnostic, prognostic, and predictive. National Comprehensive Cancer Network (NCCN) guidelines recommend that advanced practice providers conduct RAS, BRAF, HER2, and MSI testing as part of a full molecular panel, review the results, and acted on them prior to starting patients on systemic therapy.