Background This study was conducted to assess the clinicopathological characteristics of biopsy lesions in the lacrimal gland, in response to evolving pathological technologies and the emergence of new diseases. A retrospective review of case notes was conducted for 582 patients with biopsied lacrimal gland lesions at West China Hospital of Sichuan University in China. This study, spanning from January 1, 2010, to December 31, 2021, recorded demographics, clinical features, imaging findings, histopathological diagnoses, and recurrence rates. In a cohort of 582 patients, the mean age was 47.5 years, with 318 being female. Bilateral disease was present in 127 patients. Common signs and symptoms included a palpable mass, lid swelling, proptosis, and decreased ocular movements or diplopia. The predominant pathologies identified were inflammation, epithelial tumors, and lymphoproliferative lesions. Patients with inflammation (mean 32.8 months) experienced symptoms for a longer period compared to those with lymphoproliferative lesions (mean 22.2 months) (95% confidence interval [CI] 1.53–19.27, P = 0.022). Younger patients tended to have structural lesions (mean 42.5 years) (95%CI 4.74–21.59, P = 0.003), inflammation (mean 42.9 years) (95%CI 0.46–6.57, P<0.001), or epithelial tumors (mean 46.4 years) (95%CI 6.21–12.38, P<0.001), while older patients more frequently had lymphoproliferative lesions (mean 55.7 years). The period from 2016 to 2021 saw a higher diagnosis rate of biopsied lacrimal gland lesions than from 2010 to 2015. During this later period, there was an increase in cases of immunoglobulin G4-related ophthalmic disease (IgG4-ROD) and malignant epithelial tumors, while lymphoid hyperplasia cases declined. Adenoid cystic carcinoma showed the highest recurrence rate, with lesion extent and Ki-67 index identified as independent risk factors in our study. Inflammation, epithelial tumors, and lymphoproliferative lesions were the three primary causes of lacrimal gland lesions in our study group. Among the inflammatory conditions, IgG4-ROD was the most specific. The incidence of lacrimal gland lesions has risen, particularly for IgG4-ROD. Adenoid cystic carcinoma among the lacrimal gland lesions was prone to recurrence, with the extent of the lesion and Ki-67 index serving as independent risk factors.