Mycosis fungoides (MF) can progress to a large-cell malignant lymphoma (LCL). This transformation is associated with a more aggressive biologic behavior and course. We reviewed cutaneous tumors of 36 MF patients and divided them into two groups, one showing histologic evidence of transformation into LCL, another characterized by infiltrates of small- to medium-sized cerebriform cells (nontransformed cases). Biopsies of patches or plaques from early MF stages were available from 34 patients. Twenty of the 36 cases (55.6%) showed transformation to a large-cell variant: nine tumor-stage (T) medium-sized and large-cell pleomorphic, five T immunoblastic, two T large-cell anaplastic, and four unclassified T LCL. Sixteen cases represented nontransformed tumor stage MF. In 23 cases, including both nontransformed (n = 6) and LCL (n = 17) groups, immunohistochemical investigations revealed aberrant patterns of antigen expression (partial loss of one or more T cell-associated antigens) and the presence of activation- and proliferation-associated antigens. Clusters of B-lymphocytes formed a distinctive component of the infiltrate in two nontransformed and nine LCL biopsies. Although survival rates after tumor onset did not significantly differ between the two groups (5-year survival rate 23% for nontransformed patients, 11.1% for LCL patients, p greater than 0.05), overall survival from first biopsy diagnostic of MF showed a statistically significant difference between patients with nontransformed tumor stage MF compared with LCL patients (10-year survival rate 46.6% and 11.2%, respectively, p less than 0.02). The recognition of transformation to LCL in MF should provide a better assessment of future therapeutic approaches.