PURPOSE: To present 2 patients in whom orbital radiation preceded the development of periorbital extranodal marginal zone lymphoma by more than a decade and to investigate the likelihood of this representing irradiation-induced malignancy. METHODS: Retrospective chart review and histopathologic study with immunohistochemistry of 2 cases. RESULTS: The first patient was a 58-year-old woman who developed an orbital mass within the vicinity of the lateral rectus muscle 17 years after external beam proton radiation therapy for an inferotemporal choroidal melanoma. The second patient was a 32-year-old woman who developed a mass in the right lacrimal gland 12 years after external beam photon radiation therapy for chronic inflammatory dacryoadenitis. Histopathologic and immunohistochemical studies confirmed orbital extranodal marginal zone lymphoma in both cases. Retrospective review of older histopathologic slides from the second patient revealed underlying immunoglobulin G4-related disease. DISCUSSION: The unusual sequence of events in these 2 cases raises the question of whether orbital radiation may in rare instances promote the development of orbital extranodal marginal zone lymphoma. The literature pertaining to irradiation-induced secondary malignancy in the orbit is reviewed. CONCLUSIONS: Clinicians should consider the possibility of a secondary malignancy when evaluating a patient with an orbital mass and a history of prior local radiation exposure.