An unusual county-wide excess of childhood cancers of brain and other nervous tissue in the late 1990s in St Lucie County, Florida, prompted the Florida Department of Health to conduct a case–control study within the county assessing residential chemical exposures. No clear associations were found, but claims were then made that the release of radioactive substances such as strontium 90 from the St Lucie nuclear power station, which began operating in 1976, might have played a role. To test the plausibility of this hypothesis, we extended by 17 years a previous study of county mortality conducted by the National Cancer Institute. Rates of total cancer, leukaemia and cancer of brain and other nervous tissue in children and across all ages in St Lucie County were evaluated with respect to the years before and after the nuclear power station began operation and contrasted with rates in two similar counties in Florida (Polk and Volusia). Over the prolonged period 1950–2000, no unusual patterns of childhood cancer mortality were found for St Lucie County as a whole. In particular, no unusual patterns of childhood cancer mortality were seen in relation to the start-up of the St Lucie nuclear power station in 1976. Further, there were no significant differences in mortality between the study and comparison counties for any cancer in the time period after the power station was in operation. Relative rates for all childhood cancers and for childhood leukaemia were higher before the nuclear facility began operating than after, while rates of brain and other nervous tissue cancer were slightly lower in St Lucie County than in the two comparison counties for both time periods. Although definitive conclusions cannot be drawn from descriptive studies, these data provide no support for the hypothesis that the operation of the St Lucie nuclear power station has adversely affected the cancer mortality experience of county residents.