PURPOSE: To report a case initially assessed as giant papillary conjunctivitis and subsequently as B-cell lymphoma by the molecular technique of polymerase chain reaction heteroduplex analysis. DESIGN: Observational case report. METHODS: Clinical, histologic, immunohistochemical, and polymerase chain reaction heteroduplex analysis findings are presented. RESULTS: A 32-year-old man developed unilateral blepharoptosis secondary to an extensive palpebral conjunctival follicular-like process. Excisional biopsy showed a dense small lymphocyte infiltrate consistent with benign lymphoid hyperplasia by histology and immunohistologic marker studies. Polymerase chain reaction heteroduplex analysis revealed low-grade B-cell lymphoma, however. Systemic examination was negative. Focal radiation therapy was performed, and preliminary results show no signs of lymphoma. CONCLUSIONS: Polymerase chain reaction heteroduplex analysis established a diagnosis of conjunctival B-cell lymphoma in the absence of supporting histology and immunohistochemistry studies. This technique may provide independent, diagnostic distinction between benign lymphoid hyperplasia and low-grade B-cell lymphoma of the ocular adnexa.