The biology of disease progression is a complex process that involves multiple sequential steps leading to cellular changes and metabolic events. These molecular events, which may serve as potential biomarkers, can be analyzed by laboratory methods and used to detect a disease such as cancer or indicate the biological exposure to environmental substances including dietary intake. Identification of the genetic, molecular, and clinical events involved in the disease process enables the development of effective therapeutic and preventive measures and the prediction of prognostic outcomes. This article describes various factors that influence nutritional and cancer biomarker research, draws similarities between them, and discusses the measures that have been adapted to validate cancer biomarkers that can potentially be applied to nutritional biomarker research. Nutritional research suffers from a lack of means to quantify relationships between diet and cancer. Biomarkers of dietary intake or metabolism, therefore, could have potential application in study designs for establishing a causal relationship between diet and disease.