Background: Conjugated linoleic acid (CLA), a naturally occurring compound found in ruminants products, has been shown to possess anticancer properties in vivo and in vitro. There are several CLA isomers in ruminant-produced foods, among which t10, c12-CLA and c9, t11-CLA are the most potent. Protein tyrosine phosphatase gamma (PTP gamma) has been implicated as a tumor suppressor gene in kidney and lung cancers. Our previous results indicated that estradiol-17 beta (E-2)-induced suppression of PTP gamma may play a role in mammary tumorigenesis. Materials and Methods: The effects of t10, cl2-CLA and c9, t11-CLA on PTP gamma mRNA expression in human breast epithelial cells and stromal cells, isolated from surgical specimens of mammoplasty and breast cancer patients, were detected and quantified by RT-PCR. Results: The PTP gamma mRNA expression was lower in cancer than in normal breast cells. Both t10,c12-CLA and c9,t11-CLA significantly (p < 0.05) increased the PTP gamma mRNA levels in primary cultured normal breast epithelial cells, normal breast stromal cells and breast cancer epithelial cells, but not in breast cancer stromal cells. t10, c12-CLA appeared to be the most active isomer in estrogen receptor alpha(ER alpha)-positive human breast cancer epithelial cells. Conclusion: The results indicate that dietary CLA might serve as a chemo-preventive and chemo-therapeutic agent in human breast cancers by up-regulating the estrogen-regulated tumor suppressor gene, PTP gamma expression.