Cutaneous T-cell lymphoma (CTCL) is a group of slowly progressive, lymphoproliferative disorders characterized by localization of neoplastic T lymphocytes to the skin. The most common type of CTCL is mycosis fungoides which has a mild clinical course with slow and long progression. The rate of progression is generally slow and takes many years but often remains unpredictable. Special AT-rich sequence-binding protein-1 (SATB1) is a global chromatin organizer which controls gene expression by folding and remodeling chromatin, but which also regulates the level of histone methylation and acetylation, important in differentiation and apoptosis. The aim of the present study was to determine if SATB1 may be considered a prognostic and predictive factor of CTCL. The results showed that moderate and high expression of SATB1 correlate with significantly better prognosis of CTCL patients. Moreover, we showed that downregulation of SATB1 in Jurkat cells caused their resistance to activation-induced cell death. In conclusion, SATB1 expression appears to be a strong candidate as a prognostic factor confirming the inner heterogeneous features of CTCLs.