Purpose Increasing new cancer cases and approval of effective but expensive new drugs extending survival have led to unsustainable cancer care costs. Potential cost savings by a hypothetical dose down-rounding project of monoclonal antibodies at a community-based cancer center is presented. Methods From October 2014 through October 2015, metastatic cancer patients receiving monoclonal antibodies at CHI-Health St Francis Cancer Treatment Center in Grand Island, Nebraska, were identified through electronic health records. A total of 11 different types of monoclonal antibodies that were administered during the study period were identified. Trastuzumab, ofatumumab, and obinutuzumab did not require dose-rounding; thus, they were excluded from the analyses. Available vial size(s) and costs per milligram per average wholesale price for each monoclonal antibody were recorded. Costs of actual amounts prescribed were compared to the costs of theoretically reduced ≤5% and ≤10% doses rounded to the nearest vial sizes. Reduced doses resulting in a decreased number of opened vials qualified for meaningful dose down-rounding and were included in the analysis. Average actual dose reduction percentage resulting in cost savings for both groups was also calculated. Results A total of 728 doses of eight monoclonal antibodies suitable for dose down-rounding were identified. Vial sizes of pembrolizumab and ipilimumab did not allow for a meaningful dose down-rounding. At the ≤5% dose down-rounding, 255 of 728 doses (35%) qualified with a potential annual cost savings of $220,793.80. At the ≤10% dose down-rounding, 526 of 728 doses (72%) qualified with a potential annual cost savings of $454,461.00. The average actual dose reduction was 2.4% for the ≤5% dose reduction group and 4.9% for the ≤10% dose reduction group. Overall average cost savings per qualifying dose reduction was around $865.00. More doses qualified for cost savings in the ≤10% dose reduction group. Significant differences between different monoclonal antibodies for dose rounding at either ≤5% (p = 0.002) or ≤10% (p < 0.001) were observed. Conclusion A practical dose down-rounding procedure may allow significant cost reduction in metastatic cancer setting, where the cure is not the goal. Drug waste can be avoided by convenient vial sizes or can even be eliminated by lyophilized forms like in trastuzumab. Our data reflect the monoclonal antibody use and potential cost savings with the proposed dose down-rounding approach in a community-based cancer program.