Identification of quantitative changes in gene expression that occur in the malignant mammary gland, if sufficiently characterized, may yield novel molecular markers which may be useful in the diagnosis and treatment of human breast cancer. Using modifications of a previously documented technique, the differential display polymerase chain reaction, we describe the isolation of differentially expressed sequence tags, short complementary DNA fragments corresponding to mRNAs that are differentially expressed in breast cancer biopsies, as compared to normal breast tissue controls. Direct sequencing and expression analysis of two sequence tags demonstrate that they represent sequences which are overexpressed in a number of breast carcinoma cell lines. A paradigm for generating a catalogue of these sequence tags is discussed.