More than 65% of all cutaneous lymphomas are T-cell disorders. Cutaneous T-cell lymphomas (CTCL) represent a heterogeneous group of non-Hodgkin lymphomas that share the common feature of malignant T-cell infiltration of the skin (Table 10.1) [1, 2]. The most common forms of CTCL are mycosis fungoides (MF) and its leukemic counterpart Sézary syndrome (SS), accounting for ∼44% and ∼3% of cases, respectively. MF evolves through several skin-localized clinical stages (patch, plaque, and tumor stage) with extracutaneous involvement seen as a late manifestation of this disease. SS is characterized by generalized erythroderma, lymphadenopathy, pruritus, and leukemic cells in the peripheral blood, and is associated with a poorer prognosis [1, 2]. Diagnostic and staging systems for MF have historically been based on the clinical and histopathological features of the disease, and include primary tumor, lymph node, metastasis, and peripheral blood (TNMB) parameters (Table 10.2) [3, 4]. Similar to other cutaneous and systemic lymphomas, the prognosis for patients with MF is primarily related to the stage of disease at presentation [4, 5]. However, some cases, particularly early MF lesions, can demonstrate nonspecific clinical and/or histopathological features, and staging systems cannot predict outcome in all patients [4–6]. While many patients have relatively indolent disease, others experience rapidly progressive and often fatal outcomes [4, 5]. It has been proposed that ancillary molecular technologies with high sensitivities and specificities may be useful for more accurate diagnosis, staging, and prognostication of patients with MF. Based on revised International Society for Cutaneous Lymphomas/European Organization of Research and Treatment of Cancer (ISCL/EORTC) guidelines, molecular tests (Southern blot and polymerase chain reaction-based) are now recommended for the initial evaluation/staging of patients with MF [3]. It is anticipated that future studies, which incorporate these molecular techniques, will provide additional prognostic information for patients with CTCL, allowing further refinements of classification and staging guidelines [3].