Mycosis fungoides (MF), the most common primitive cutaneous T-cell lymphoma, can undergo transformation in about 10% of cases. Transformed mycosis fungoides (T-MF) is often associated with the appearance of a CD20 component. The aim of this study was to analyze whether such cells are reactive or lymphomatous and to evaluate their prognostic impact. Among 311 T-MFs from the French Cutaneous Lymphoma Study Group registry, we studied 148 cases. CD20 was expressed in 88 cases (59%). The proportion of CD20 cells among T-MF lesions was <10% for 54 cases (38%), 10% to 49% for 71 cases (81%), and >50% for 17 cases (19%). We focused the study on 23 cases that contained >50% CD20 cells. To evaluate the nature of the CD20 component, we used immunohistochemistry (2 anti-CD20 antibodies, L26 and 7D1 clones, and 2 other anti-B-cell antigen antibodies, CD22 and PAX5) and a double-stain immunofluorescence technique (anti-CD20 and anti-CD3 antibodies). The clonality of B cells was studied by polymerase chain reaction. Three profiles were observed. In 15 of the 23 cases, the CD20 cells were reactive. In 6 cases, CD20 protein was aberrantly expressed in T-MF lesions. Lastly, there were 2 composite lymphomas (T-MF infiltrate with a B-cell follicular lymphoma). In view of this series, we propose a simple algorithm to help pathologists evaluate the nature of the CD20 component associated with T-MF. Although statistically not significant, there was a trend toward a worse prognosis in the presence of >50% CD20 cells and of a nodular perifollicular pattern of this component.