The diagnostic and prognostic importance of recurrent chromosomal aberrations in systemic B cell lymphoma is well documented. In contrast, limited data exist on genetic changes in primary cutaneous B cell lymphoma. In this study we investigated chromosomal aberration patterns in two types of primary cutaneous B cell lymphoma with a different clinical behavior. Twenty-two primary cutaneous B cell lymphomas, including nine follicle center cell lymphomas and 13 large B cell lymphomas of the leg, were analyzed by comparative genomic hybridization and in part by fluorescence in situ hybridization. The most frequent imbalances detectable were gains in 18q (eight of 22), 1q (six of 22), 7 (six of 22), 12q (six of 22), or Xp (four of 22), and losses in 6q (four of 22). In contrast to large B cell lymphomas of the leg, primary cutaneous follicle center cell lymphomas had fewer imbalances and lacked translocations affecting the IGH locus. Gains in 18q (eight of 13) and losses in 6q (four of 13) as well as breakpoints within the IGH locus (six of 11) were restricted to the large B cell lymphomas of the leg subtype. Translocation t(14; 18) was excluded in 16 primary cutaneous B cell lymphomas of both subtypes that were studied by fluorescence in situ hybridization. These results suggest that primary cutaneous follicle center cell lymphoma and large B cell lymphoma of the leg are characterized by different chromosomal aberration patterns, which in part might determine the different clinical course of these malignancies.