In mycosis fungoides (MF) with blood involvement, T-cell immunophenotypes in skin and blood have not been compared. Our aim was to evaluate T-cell immunophenotypes in skin by immunohistochemical analysis and compare results with flow cytometric (FC) findings in blood. Of 20 patients with MF with blood involvement, the immunophenotype was discrepant in 11 (55%). Compared with FC findings in blood, immunohistochemical analysis of skin samples failed to detect partial deletion of CD2 (5/11 [45%]), CD3 (3/11 [27%]), and CD5 (3/11 [27%]) and overrepresented deletion of CD7 in 2 (18%) of 11 patients. In addition, CD8+ MF was missed by immunohistochemical analysis in 2 (18%) of 11 patients. Identical T-cell populations were demonstrated by T-cell gene polymerase chain reaction in skin and blood in 8 of the 11 patients who had a discrepant immunophenotype. Awareness of the limitations of immunohistochemical analysis of skin samples is of practical value for pathologists interpreting skin biopsies in MF patients. In addition, our findings suggest CD8+ MF to be more common than previously reported.