BACKGROUND: Obesity has been linked to abnormal estrogen regulation, endometrial hyperplasia, and endometrial cancer (EC). Our group has shown that hormone receptor expression profiles in the endometria of morbidly obese women change with weight loss, in some cases concordantly with resolving hyperplasia; however other potential drivers of neoplasia, including altered immunologic tolerance exist. The objective of this study was to evaluate the effect of bariatric surgery induced weight loss on the expression patterns of nonhormone receptor biomarkers associated with cancer and immunity. METHODS: Endometrial biopsies were obtained from 59 asymptomatic, morbidly obese women at the time of bariatric surgery and again 1 year postsurgery. Tissue microarrays were created and immunohistochemical stains for CD3, CD20, and PTEN were performed on all samples and evaluated by 2 blinded pathologists independently. Approximately 50% of participants had sufficient tissue for analysis at both visits. McNemar/Bowker tests of symmetry were performed to compare proportions between categories for matched pairs (pre- and post-treatment). RESULTS: Endometrial hyperplasia was identified in 4 women despite negative clinical histories and resolution of hyperplasia after weight loss occurred in 3 women. While overall no significant differences were observed between matched pre and postsurgery levels of CD20 and CD3 positive cells, a tendency toward decreased expression levels from baseline status was observed for CD20. No differences were observed for PTEN. CONCLUSION: Our data demonstrate that the prevalence of endometrial pathology appears to be partially mitigated by weight loss. Weight loss is associated with alterations in the hormone receptor profiles, but these data suggest that changes in the immune response, as measure be expression of CD20+, may be relevant targets for EC prevention research.