Background: Diagnosis of cutaneous lymphoma in the absence of systemic lymphoma may be difficult. Reactive lymphoid lesions can mimic lymphoma clinically and histologically and have been designated pseudolymphomas. Objective: Our purpose was to analyze lymphoid gene rearrangements in cutaneous lymphoproliferative lesions and to correlate these findings with the histologic, immunophenotypic, and clinical profile. Methods: We examined 21 cases of lymphoproliferative lesions that developed in skin and performed molecular rearrangement analysis of T-cell receptor and immunoglobulin genes. We examined identical tissues by histologic and immunophenotypic criteria and conducted follow-up clinical evaluation of all patients. Results: Clonal rearrangements of immunoglobulin (seven cases) or T-cell receptor (two cases) gene were detected in 9 of 21 patients. No specific histologic or immunophenotypic feature was consistently associated with a clonal lymphoid gene rearrangement. Systemic lymphoma developed in one patient in whom a clonal rearrangement within the immunoglobulin gene was identified. Conclusion: Gene rearrangement analysis may be helpful in differentiating primary cutaneous lymphoma from pseudolymphoma. The chronic clinical course of patients with clonal lymphoid gene rearrangements supports a lack of correlation between clonality and biologic aggressiveness.