We investigated the clinical, morphologic, immunologic, and molecular genetic characteristics of the lymphoid tumors occurring in 17 patients with bilateral ocular adnexal lymphoid neoplasia. We found no obvious differences in the age, sex, clinical appearance, or ophthalmic findings between patients with unilateral and those with bilateral ocular adnexal lymphoid neoplasms. Five orbital and two conjunctival lymphoid neoplasms removed from five patients were polyclonal pseudolymphomas, while nine orbital, eight conjunctival, and two eyelid lymphoid neoplasms removed from 12 patients were monoclonal B cell non-Hodgkin's lymphomas. Each pair of simultaneously bilateral lesions occurring in a single individual was morphologically and immunologically identical and exhibited identical immunoglobulin gene DNA rearrangement patterns. None of the five patients with polyclonal pseudolymphomas developed nonocular non-Hodgkin's lymphoma, but one developed a contralateral conjunctival monoclonal B cell non-Hodgkin's lymphoma. Six of the 12 patients with ocular adnexal monoclonal B cell non-Hodgkin's lymphomas developed nonocular non-Hodgkin's lymphoma. The incidence of previous or subsequent systemic nonocular non-Hodgkin's lymphoma in patients with bilateral ocular adnexal lymphoid neoplasms is comparable to that of patients with unilateral disease. In both patient groups, the development of nonocular non-Hodgkin's lymphoma is most commonly associated with ocular adnexal lymphoid neoplasms displaying follicular or diffuse small cleaved cell (poorly differentiated lymphocytic) morphologic characteristics.