Cutaneous T cell lymphomas (CTCL) are a diverse group of lymphoid malignancies that develop in the skin. The most common variants are mycosis fungoides (MF) and Sezary syndrome (SS). These skin lymphomas can be challenging to differentiate from non-malignant inflammatory skin disorders such as psoriasis or nummular eczema, thus the identification of biomarkers is important in early diagnosis and treatment. Gene expression analysis has identified novel genes that are expressed in MF/SS that may improve diagnosis of MF/SS. Although the catalog of biomarker genes remains incomplete, a mechanism playing a role in the increased expression of biomarkers in MF/SS includes epigenetic changes. This is supported by the efficacy of evolving therapeutic strategies that modulate gene regulation, such as HDAC inhibitors and methylation inhibitors in the treatment of this group of cancers.