We performed a prospective multiparametric correlative clinical, histopathologic, and immunologic analysis of 117 ocular adnexal lymphoid proliferations developing in 108 patients between October 1977 and July 1987. The ocular adnexal lymphoid proliferations were distributed among the 108 patients as follows: orbit 69 (64%), conjunctiva 30 (28%), and eyelids nine (8%). The 117 ocular adnexal lymphoid proliferations were classified as follows: polyclonal lymphoid hyperplasia, 32 (22 orbit, nine conjunctiva, one eyelid) (27%); monoclonal B cell lymphoma, 81 (48 orbit, 25 conjunctiva, eight eyelid) (69%); null cell lymphoma, one (orbit) (1%); and histologically indeterminate, three (one each: orbit, conjunctiva, eyelid) (3%). Patients presenting with ocular adnexal polyclonal lymphoid hyperplasia and monoclonal B cell lymphoma, and patients developing unilateral and bilateral ocular adnexal lymphoid proliferations did not differ significantly with respect to age, sex, presenting complaints, duration of symptoms, or ophthalmic findings. Classifying ocular adnexal lymphoid proliferations into benign and malignant categories by histopathologic criteria and into polyclonal and monoclonal B cell categories by immunophenotypic criteria was not useful in predicting eventual outcome, including the occurrence of extraocular lymphoma. However, the clinicopathologic characteristics did differ according to the anatomic site of involvement and histopathology of the ocular adnexal lymphoid proliferations. Lymphoid infiltrates of the conjunctiva were associated with a lower incidence of extra-ocular lymphoma (20%) than were those of the orbit and eyelid, 35% and 67%, respectively (statistically significant, P less than .03). Ocular adnexal small lymphocytic and intermediate lymphocytic lymphomas were less often associated with extra-ocular lymphoma than were ocular adnexal lymphomas of all other histologic types, 27% and 46%, respectively (P less than .09). However, the single most important and statistically significant prognostic factor in these patients was the extent of disease at the time of presentation with an ocular adnexal lymphoid proliferation (P less than .001). Eighty-six percent of patients presenting with a unilateral or bilateral clinical stage lE ocular adnexal lymphoid proliferation, regardless of the histopathology or the immunophenotype, had a benign indolent clinical course and failed to develop ocular or extra-ocular lymphoma during a median follow-up period of 51 months. The results of this study substantially improve our understanding of extranodal small lymphocytic proliferations in general, and those of the ocular adnexa in particular.