Introduction:Drugs may be an important cause of atypical lymphocytic infiltration.Often times,these infiltrates are in the context of pseudolymphomata.We report a patient who developed lymphocytoma cutis temporally associated with initiation of fluoxetine therapy that later went on to develop cutaneous marginal zone B-cell lymphoma.The response of peripheral blood lymphocytes to fluoxetine and other drugs was examined in an attempt to ascertain the potential role for drugs in the propagation of these infiltrates.Materials and Methods:Routine light microscopic analysis and phenotypic studies were performed on tissue obtained from a skin biopsy.Lymphocyte mitogenic studies were carried out using increasing concentrations of fluoxetine,bupropion,and two anticonvulsants.Results:An initial biopsy was consistent with lymphocytomacutis.The patient stopped fluoxetine associated with lesional regression.The lesions recurred despite being off fluoxetine;a repeat biopsy was compatible with marginal zone lymphoma.Lymphocyte proliferation assays revealed a suppressive effect on T-lymphocyte proliferation at physiologic concentrations.Other tested drugs did not have a similar suppressive effect.Conclusion:Fluoxetine may be associated with pseudolymphomata and marginal zone lymphoma.The inhibitory effects on T-lymphocyte function and more specifically T-suppressor function may lead to excessive antigen-driven B-cell proliferation. Introduction: Drugs may be an important cause of atypical lymphocytic infiltration. Often times, these infiltrates are in the context of pseudolymphomata. We report a patient who developed lymphocytoma cutaneous temporally associated with initiation of fluoxetine therapy that later went on to develop cutaneous marginal zone B -cell lymphoma. The response of peripheral blood lymphocytes to fluoxetine and other drugs was examined in an attempt to ascertain the potential role for drugs in the propagation of these infiltrates. Materials and Methods: Routine light microscopic analysis and phenotypic studies were performed on tissue obtained from a skin biopsy. Lymphocyte mitogenic studies were carried out using increasing concentrations of fluoxetine, bupropion, and two anticonvulsants. Results: An initial biopsy was consistent with lymphocytomacutis. The patient stopped fluoxetine associated with lesional regression. The lesions recurred despite being flu fluetetine; a repeat biopsy was compatible with margin al zone lymphoma. Lymphocyte proliferation assays revealed a suppressive effect on T-lymphocyte proliferation at physiologic concentrations. Other tested drugs did not have a similar suppressive effect. Confc: Fluoxetine may be associated with pseudolymphomata and marginal zone lymphoma. inhibitory effects on T- lymphocyte function and more specifically T-suppressor function may lead to excessive antigen-driven B-cell proliferation.