Cutaneous T-cell lymphoma (CTCL) is a clonally derived lymphoproliferative disorder that preferentially involves the skin. The two major clinical expressions of CTCL, mycosis fungoides (MF) and Sézary syndrome (SS), have poorly understood pathogenesis. Chromosome abnormalities, mostly complex karyotypes, are seen in about 50% of patients with MF/SS, and there have only been a few instances of recurrent rearrangements. We analyzed 19 blood samples from patients with MF/SS with cytogenetics and multicolor FISH (SKY) to better describe the complex karyotypes and search for recurrent abnormalities or breakpoints. Comparison of phytohemagglutinin (PHA)-stimulated cultures versus a combination of interleukin 2 plus interleukin 7 showed similar efficiency in detecting abnormal clones; however, the PHA cultures yielded more analyzable metaphases. Nine of 19 patients (47%) had an abnormal karyotype. The most frequent abnormalities, in 7 of 9 cases, involved chromosome 10; followed by chromosome 6, in 6 of 9 cases; chromosomes 3, 7, 9, 17, and 19, in 5 of 9 cases; chromosomes 1 and 12, in 4 of 9 cases; and chromosomes 8, 11, and 13, in 3 of 9 cases. Most abnormalities were structural. Recurrent rearrangements included deleted chromosomes 6 and 13, in three cases each, and recurrent breakpoints at 1p32-36, 6q22-25, 17p11.2-13, 10q23-26, and 19p13.3, occurring in three or more cases. One patient had a pseudodicentric translocation between the short arms of chromosomes 8 and 17, confirmed by dual-color FISH and interpreted as psu dic(17;8)(p11.2;p11.2). Two patients with SS reported in the literature seem to have a similar translocation. If confirmed, a psu dic(17;8) could be the first recurring translocation detected in at least three patients with MF/SS.