Potato cyst nematodes (PCN) (Globodera spp.) are quarantine pests with serious potential economic consequences. Recent new detections in Australia, Canada, and the United States have focussed attention on the consequences of spread and economic justifications for alternative responses. Here, a full assessment of the economic impact of PCN spread from a small initial incursion is presented. Models linking spread, population growth, and economic impact are combined to estimate costs of spread without restriction in Australia. Because the characteristics of the Australian PCN populations are currently unknown, the known ranges of parameters were used to obtain cost scenarios, an approach which makes the model predictions applicable generally. Our analysis indicates that mean annual costs associated with spread of PCN would increase rapidly initially, associated with increased testing. Costs would then increase more slowly to peak at over AUD$20 million per year ≈10 years into the future. Afterward, this annual cost would decrease slightly due to discounting factors. Mean annual costs over 20 years were $18.7 million, with a 90% confidence interval between AUD$11.9 million and AUD$27.0 million. Thus, cumulative losses to Australian agriculture over 20 years may exceed $370 million without action to prevent spread of PCN and entry to new areas.