Mummichogs Fundulus heteroclitus were collected in 2002-2004 from six locations within the Delaware Estuary watershed and examined histopathologically. The objective was to compare the prevalence of skin and liver tumors in fish from locations with a range of sediment polynuclear aromatic hydrocarbons (PAHs) based on available data. Fish were collected from (1) three locations within the industrialized Christina River subwatershed (Hershey Run, Newport Marsh (upriver and downriver)); (2) one location in the Motiva Enterprises refinery discharge canal to the Delaware River; (3) one location in the St. Jones River; and (4) one location in Blackbird Creek. Adult mummichogs (≥70 mm; n = 21-30 fish per location) were seined and held for necropsy. No neoplastic skin lesions were diagnosed in any fish. No liver tumors were diagnosed in the St. Jones, Motiva, Newport Marsh upriver, or Newport Marsh downriver collections. One of 30 Blackbird Creek mummichogs had foci of hepatocellular alteration (a putative preneoplastic lesion) and one had hepatocellular carcinoma. There was a significant difference in hepatocellular carcinoma prevalence in Hershey Run mummichogs in 2002 (9 of 21 fish, or 43%) and in 2003 (3 of 29 fish, or 10%) compared with all other locations pooled (1 of 145 fish, or 0.7%). Hershey Run is contaminated with creosote from an adjacent Superfund site, where sediments were frequently reported to have total PAH concentrations greater than 100 mg of total PAH/kg and a maximum of 13,300 mg/kg. No other locations had reports of total PAHs higher than 11 mg/kg. In conclusion, liver neoplasia was associated with exposure to sediment containing high concentrations of PAHs derived from creosote. Studies that include tumor prevalence, biomarkers (e.g., DNA adducts and PAH metabolites in bile), and sediment and/or tissue chemistry are recommended to develop a weight of evidence for specific chemical classes.