In Spring 2011, 200 adult white sucker were collected in four areas of the St. Louis River area of concern (AOC), located in Minnesota and Wisconsin, USA. The areas included the upper AOC as a reference area, the upper estuary, St. Louis Bay and Superior Bay. Grossly visible abnormalities were documented and preserved for microscopic analyses, as were five to eight representative pieces of liver tissue. A piece of dorsal muscle was preserved for stable isotope analyses and otoliths removed for age determination. The incidence of raised skin lesions (mucoid plaques) was high (31 %), however, microscopically only 4.5 % of the white suckers had neoplasia (papillomas). The remaining lesions were epidermal hyperplasia. Superior Bay had the lowest percentage of skin/lip lesions (10 %), while St. Louis Bay had the highest (44 %). St. Louis Bay also had the highest incidence of skin neoplasms (12 %). No hepatocellular neoplasms were documented, however bile duct tumors were observed in 4.5 % of the suckers. Foci of cellular alteration were observed in fish from all sites except the upper AOC. Stable isotope data indicated that most of the suckers relied on the St. Louis River AOC for the majority (>75 %) of their diet, indicating they were resident within the AOC and not in Lake Superior. The amount of diet obtained from the upper estuary was a significant predictor of skin lesion incidence. Hence, habitat use within the AOC appears to be an important risk factor for skin and possibly, liver lesions.