According to the European Organization for Research and Treatment of Cancer classification, primary cutaneous follicle center cell lymphoma is not associated with the t(14;18)(q32;q21) and only rarely expresses bcl-2 protein. To further investigate this issue, we evaluated a series of 20 patients (14 men, 6 women) with primary cutaneous follicular lymphoma (PCFL). The presenting skin lesion was located in the head and neck region in 16 of 20 patients. Most cases were grade 2 (6/20) or grade 3 (13/20), and all had a follicular architecture. Immunohistochemical analysis demonstrated bcl-2 expression in 8 cases (40%), and expression was inversely related to the grade. Of 7 grade 1 or 2 cases, 5 (71%) were positive, whereas only 3 (23%) of 13 grade 3 cases were positive for bcl-2. Clonal immunoglobulin heavy chain gene rearrangements were detected in 9 (45%) of 20 cases. In 4 (20%) of 20 cases, we identified the major breakpoint of the t(14;18) by polymerase chain reaction, 3 of which were grade 1 or 2. We conclude that bcl-2 protein expression and the t(14;18) are present in a subset of PCFL, particularly in lower grade cases.