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Background: Over the last few decades, Reflectance Confocal Microscopy (RCM) has been tested as a diagnostic technique and recently, demonstrates effectiveness to monitor the therapeutic response in melanoma and non-melanoma skin cancer, but it has not been used for follow-up in Cutaneous Lymphoma. This innovative technology allows an in vivo dynamic evaluation of multiple lesions and helps to identify areas of active disease. Moreover, the non-invasive nature of this technique allows repetitive sampling without biopsy collection, causing no further morbidity to patients. Its main advantage is the possibility of risk-free longitudinal monitoring. Objective: Our aim was to evaluate the role of RCM in the follow-up of patients with Mycosis Fungoides (MF). Additionally, to correlate RCM features with clinical and histopathological features before and after treatment. Method: Patients were assessed with RCM on the same site that diagnostic biopsies were performed and re-assessed 6 months after treatment. RCM descriptors were defined by a systematic review. Histopathological correlation and clinical correlation were assessed. Results: A total of 30 patients were assessed by RCM and biopsies were taken in 38 lesions. After 20 to 30 weeks under treatment, 19 lesions were re-assessed by RCM and 12 were re-biopsied. RCM demonstrated good correlation with clinical and histopathological assessments with 4 RCM parameters (epidermotropic lymphocytes, Pautier’s microabscess, interface dermatitis and junctional lymphocytes) achieving an AUC 0.955 (SD: 0.053, p: 0.003). Conclusion: RCM is an excellent tool to assess the response of skin lesion in patients with MF, with excellent correlation with clinic and histological assessment. Keywords: Follow up, Score, Cutaneous T-cell lymphoma, Skin cancer, Reflectance Confocal Microscopy, Mycosis Fungoides more...