A conclusive fish tumour prevalence assessment has never been conducted in the lower part of the St. Clair River Area of Concern, despite possible re-contamination of the river and anecdotal evidence of fish abnormalities. This paper provides a study design for a comprehensive fish tumour prevalence assessment of the Lower St. Clair River with special focus on Walpole Island First Nation and surrounding waters. Study details such as area of focus, sentinel species, suggested sampling locations, sample size, field protocols and statistical methods are identified. A brief guide for histopathological examination and interpretation is provided. An alternate method of sampling location siting is suggested. This study design is intended to provide a guide and background reference for the implementation of a future full scale fish tumour assessment in the Lower St. Clair River.