This document provides methods and materials involved in removing polypeptides (e.g., high abundance polypeptides) from stool samples. For example, methods and materials for preparing a stool sample for detecting polypeptides of low abundance are provided. For example, this document provides methods and materials for depleting abundant polypeptides common to stool from normal, healthy humans from a stool sample. Such depleted stool samples can be used to detect polypeptides of interest such as low abundance polypeptides or neoplasm-specific polypeptide markers that can be present in a mammal suffering from a disease such as cancer.