Background: The role of regulatory T cells (Tregs) in mycosis fungoides (MF)yielded discordant findings. Moreover, aberrant Cyclooxygenase-2 (COX-2)expression has been implicated in tumorigenesis and it was shown that COX-2is ectopically expressed in malignant T-cell lines from patients with MF.Aim of study: To clarify the role of both Tregs as identified by FOXP-3 andCOX-2 expression in the immunopathogenesis of MF and to study the relationbetween both entities in order to implement new strategies in the managementof MF.Patients and methods: This prospective comparative study included 30 MFpatients and 20 controls. Skin biopsies were divided into 2 parts;1st part wasexamined for detection of FOXP3 percent area by immunohistochemistry and2nd part was examined for gene expression of FOXP3 and COX-2 by real timePCR.Results: The mean area percent, tissue expression of FOXP3 and COX-2 inMF patients (44.617±11.807, 1.13±0.49, 0.28±0.213) were significantly higherthan controls (14.136±3.949, 0.141±0.076, 0.003±0.003) (P<0.001). In MF asignificant positive correlation between the measured FOXP3 mean area % andtissue levels of both FOXP3 and COX2 was detected. On comparing theirlevels in relation to the different staging of MF a statistically significantdifference (P<0.001) with the highest values were detected in patients withstage III and the lowest values in patients with stage Ia.Conclusions: Increased expression of both FOXP3 and COX2 in MF incomparison to controls, together with their positive correlation with each otherand with the disease staging was documented in the current study, suggestingan important role played by the interplay between immunosuppression(FOXP3) and persistent inflammation (COX2) in the complex pathogenesis ofMF.