Background: Orbital idiopathic inflammation, lymphoid hyperplasia, and lymphoma may all present clinically in the same manner. Histopathology and especially immunohistochemistry play a major role in the differential diagnosis.The purpose of this study was to determine the immunophenotypic features of these lesions. Methods: Fifty-five orbital lymphoid lesions were retrieved from the ophthalmic pathology registries at McGill University, Montreal, Canada, and the Federal University of São Paulo, São Paulo, Brazil. Formalin-fixed, paraffin-embedded, histopathologic sections were stained with hematoxylin and eosin and periodic acid-Schiff. The sections were also immunostained for B-cell (CD20) and T-cell (CD43) markers and for immunoglobulin light chains kappa and lambda. Two pathologists determined the histopathologic and immunohistochemical pattern of each lesion in a masked fashion. Results: Of the 55 lesions, II (20%) were idiopathic chronic inflammations, 22 (40%) were lymphoid hyperplasias and 22 (40%) were lymphomas. Idiopathic inflammation displayed a predominance ofT cells and all lesions expressed polyclonal light chains. Lymphoid hyperplasia displayed a mixture of B cells and T cells, with a slight predominance of the former and all lesions expressed polyclonal light chains. Lymphoma showed a striking predominance of B cells and all lesions expressed monoclonal light chains, usually kappa (63.7%). The differences in the mean percentages of B cells among the orbital lymphoid lesions (inflammation, 35%; hyperplasia, 65.9%; lymphoma, 87.3%) were statistically significant ( p < 0.001). Interpretation: Orbital lymphoid lesions can be differentiated based on the percentages of B cells and T cells and the monoclonal or polyclonal expression of immunoglobulin light chains.