Background/Objectives <p>To characterise the clinical, radiological and histopathological features of biopsied lacrimal glands in a Japanese population and to identify clinical parameters that may assist in differential diagnosis.</p> Subjects/Methods <p>This retrospective review included consecutive patients who underwent incisional lacrimal gland biopsy between January 2016 and August 2025 at a tertiary referral centre in Japan. Clinical, imaging and laboratory data, along with histopathologic diagnoses, were analysed. Lacrimal gland dimensions were measured on orbital images and comparative statistical analyses were performed among major diagnostic groups.</p> Results <p>A total of 128 patients were included. The most frequent diagnosis was immunoglobulin G4-related ophthalmic disease (IgG4-ROD, 44.5%), followed by idiopathic orbital inflammation (IOI, 25.7%), lymphoproliferative disorders (20.3%) and other specific inflammatory dacryoadenitis (9.3%). IgG4-ROD and lymphoma showed significantly higher rates of systemic involvement compared with IOI (<i>P</i> = 0.015) and bilateral disease was more common in IgG4-ROD (<i>P</i> = 0.010). Lacrimal gland size tended to be larger in lymphoma and IgG4-ROD. Of 58 bilateral cases biopsied on both sides, 57 showed identical histopathologic findings.</p> Conclusion <p>IgG4-ROD was the leading cause of lacrimal gland enlargement in this Japanese cohort, suggesting a higher prevalence than in other populations. Integrating clinical factors such as age, laterality and systemic involvement enhances diagnostic accuracy. Unilateral biopsy is generally sufficient in bilateral cases.</p>