We have investigated the HECA-452 expression in large plaque parapsoriasis (PP) and mycosis fungoides (MF) patients, evaluating the potential role of this biomarker in both cutaneous disorders. Skin specimens from 72 PP and 61 MF patients were selected in this study. We compared their actual histological diagnosis with their previous diagnosis and we found that all 72 PP patients had the same diagnosis as before (stable PP), while 26 out of 61 MF have a previous PP histological diagnosis (evolving PP). Our results show an increased expression of HECA-452 in MF compared to PP (p<0.01). Furthermore, evolving PP showed a significantly higher level of HECA-452 than stable PP (p< 0.05). We conclude that HECA-452 expression increases during the natural history of Mycosis Fungoides. HECA-452 could be used as a biomarker for MF and predict which PP evolves to MF.