Abstract The mammalian target of rapamycin (mTOR) signaling pathway is upregulated in the pathogenesis of many cancers, including cutaneous T cell lymphoma. DEPTOR is an mTOR binding protein and endogenous mTOR inhibitor. However, the significance of DEPTOR in the development of mycosis fungoides (MF) is not known. This study aimed to investigate the possible role of DEPTOR in the pathogenesis of MF. Forty patients with MF and 40 healthy controls were included in the study. Serum fasting DEPTOR levels of the study groups were examined by enzyme-linked immunosorbent assay. The mean serum DEPTOR levels were significantly lower in patients with MF than controls (p<0.05). In conclusion, DEPTOR is possibly a novel tumor suppressor protein in MF. DEPTOR reactivation may be a potential therapeutic approach for patients with MF.