Cancer is the most common fatal disease among US children. The fetus has reduced resistance to toxic injury and is especially prone to mutagenic injury because of the high rate of cell division. A fetus can be exposed to environmental toxins through maternal consumption of contaminated water. The objective of this study was to estimate the incidence risk for childhood cancers within each watershed in Texas. The approach modeled risk for 19 cancer histotypes incorporating correlations among the cancer types and spatial correlation. Several watersheds in a very large area known as the Central Great Plains of North Texas were associated with increased risk for astrocytoma. Two watersheds near Houston, Buffalo–San Jacinto and West Galveston Bay, had increased risk for renal cancer and acute lymphoid leukemia, respectively. A watershed in South Texas, the South Laguna Madre, had increased risk for atypical leukemias. The possibility that waterborne toxins cause these childhood cancers should be investigated further.