We report the reclassification according to recently described histologic categories of 48 patients with ocular adnexal lymphoproliferative lesions with long-term follow-up (mean, 8.1 yr). We used available formalin-fixed, paraffin-embedded, and frozen tissues to assess the frequency of immunoglobulin heavy chain gene rearrangement detectable by polymerase chain reaction in these lesions. We reviewed patient records, obtained follow-up data, and examined hematoxylin- and eosin-stained slides. DNA extracted from tissues was amplified with consensus V- and J-region primers to detect immunoglobulin heavy chain gene rearrangement. We examined 28 orbital, 10 lacrimal, and 10 conjunctival lesions, of which 2 lesions were lymphoid hyperplasias, 3 were indeterminate, and 43 were lymphomas. Of the 44 patients with follow-up, systemic lymphoma developed in 24 (55%), of whom 11 died of the disease, and 6 are alive with disease. Thirty-one patients had sufficient DNA for polymerase chain reaction analysis; 9 specimens were nonclonal, 21 were clonal, and 1 failed to amplify. The nonclonal lesions included one hyperplasia, one indeterminate lesion, and seven lymphomas; two of these patients died of the disease, and one is alive with disease. The clonal lesions included 1 indeterminate lesion and 20 lymphomas. Systemic lymphomas developed in 16 patients; 8 died of the disease, and 4 are alive with disease. Of the lesions histologically classified as lymphoma, 74% were clonal. We conclude that most ocular adnexal lymphoproliferative lesions can be histologically classified as lymphomas, that systemic lymphoma will develop in at least 50% of these patients if they are followed for sufficient time, and that most lesions classified as lymphomas will be clonal using polymerase chain reaction techniques. Lack of amplification using a consensus primer strategy may account for the inability to detect clonality by polymerase chain reaction in some histologically identified lymphomas.