Primary cutaneous T-cell lymphoma (CTCL) is responsible for two-thirds of cutaneous lymphoma cases. Mycosis fungoides (MF), the most common subtype of CTCL comprises approximately 60% of CTCLs. Due to the similar clinical features of MF and inflammatory diseases such as eczema and psoriasis, early-stage MF can easily be misdiagnosed as chronic inflammatory dermatoses, posing a diagnostic challenge to the dermatologist. Early-stage MF is characterized by a favorable prognosis with long-term survival similar to or slightly lower than that of age-matched healthy people, with a 5-year survival between 88% and 100%. In contrast, advanced-stage MF shows aggressive progression, and the median survival time of patients with lymph node and visceral involvement is only 13 months. Therefore, it is important to achieve early diagnosis to improve prognosis, yet there are few specific biomarkers for the early diagnosis and prognosis of MF. In this study, we described the pathological features of MF during the early and advanced stages through proteomics technology, providing clues for the pathogenesis of MF as well as biomarkers for malignant tumors in the early stage. More importantly, diagnostic biomarkers of early-stage MF were identified by comparing the proteomic characteristics of early-stage MF and inflammatory diseases, with the goal of preventing delayed therapy due to misdiagnosis.