Background: Although mycosis fungoides (MF) is considered to be the commonest form of primary cutaneous T-cell lymphomas (CTCL), several gaps are still present in our understanding of the etiology, pathogenesis and prognosis of MF, and current treatment modalities are mainly stage based and seem to only control the disease. Endocan emerged in the past years as a reliable prognostic factor in several cancers, and was tied to the pathogenesis of cancers; hence endocan represents a promising therapeutic target for cancers in the future. Aim: The aim of this work is to study the levels of endocan in the serum and tissue of M.F patients of different stages in comparison to controls, and also to compare these levels among different stages of M.F patients, in order to detect the possibility of using endocan as a prognostic factor in M.F. Materials and Methods: Twenty five patients with MF and fifteen age and sex matched healthy controls were enrolled in the study. The tissue and serum expression of Endocan (ESM-1) were measured using enzyme-linked immunosorbent assay (ELISA) technique. Results: The mean tissue level of ESM-1 was significantly higher in patients (2907.8 ± 4575 pg/gm), than in controls (59.1 ± 15 pg/gm) (p < 0.001). A strong positive statistical correlation was detected between the tissue ESM-1 levels of MF patients and the stage of the disease (p < 0.001, r=0.658), also with the extent of lesions in MF patients (p < 0.001, r=0.771). A statistically significant rise was detected in the tissue ESM-1 levels compared (mean value 2907.8 ± 4575) to the serum ESM-1 levels in MF patients (mean value19.9 ± 71.7, p < 0.001), with a positive statistical correlation (p= 0.024, r= 0.449). The mean serum ESM-1 level was not statistically significant in patients (19.9 ± 71.6 pg/ml), compared to controls (7 ± 2.8 pg/ml) (p = 0.086). No statistically significant correlation was detected between the serum ESM-1 levels and the stage of the disease (p= 0.218). Conclusion: These study findings prove that tissue endocan or ESM-1 levels are elevated in MF patients, and are positively correlated to the clinical stage of the disease and with the extent of lesions, suggesting its possible role as a prognostic factor in MF.