Clinical decision support (CDS) within the electronic health record represents a promising mechanism to provide important genomic findings within clinical workflows. To better understand the current and possible future costs of genomic CDS, we leveraged our local CDS experience to assemble a simple model with inputs such as initial cost and numbers of patients, rules, and institutions. Our model assumed efficiencies of scale and allowed us to perform a one-way sensitivity analysis of the impact of each model input. The number of patients with genomic results per institution was the only single variable that could decrease the cost of CDS per useful alert below projected genomic sequencing costs. Because of the prohibitive upfront cost of sequencing large numbers of individuals, increasing the number of institutions using genomic CDS and improving the efficiency of sharing CDS infrastructure represent the most promising paths to making genomic CDS cost-effective.