Levels and activity of the enzyme estrogen sulfotransferase (EST) have been reported to play an important role in the regulation of in situ estrogen levels in human breast, prostate, and endometrial cancer. To better understand growth progression in endometrial stromal sarcomas (ESS), estrogen-dependent tumors, we analyzed the expression of EST in a series of 29 ESS. Archival formalin-fixed, paraffin-embedded material was analyzed immunohistochemically with a monoclonal antibody to EST using the peroxidase-antiperoxidase method. A score was calculated based on the percentage of positive tumor cells and staining intensity. EST staining was identified in 5 of 29 (18%) ESS and was scored as weakly positive, while 24 of 29 (82%) ESS were negative for EST. We demonstrate that a subset of ESS express EST, which may allow them to inactivate intratumoral estrogens. ESS without EST expression may have increased levels of biologically active estrogen, which explains the tumor progression of this entity and these patients may be at increased risk for recurrences and metastases.