The most common lacrimal sac pathology is chronic inflammation with or without occlusive fibrosis. However, a substantial number of lacrimal sac-specific pathologies were reported throughout the literature which may mimic chronic inflammation and be misdiagnosed. From a tertiary ophthalmic care centre in Serbia, in a single ophthalmic pathology laboratory, during a 7-year period (January 2004 to October 2010), a 599 consecutive lacrimal sac wall biopsy samples routinely obtained during external dacryocystorhinostomy in adult patients with clinically presumed primary acquired lacrimal drainage system obstruction were analysed. Although non-specific lacrimal sac pathology was present in the vast majority of cases (578 biopsy specimens; 96.49%), this report also reveals a relatively substantial number (21 biopsy specimens; 3.51%) of clinically non-suspected or intraoperatively unexpected primary lacrimal sac-specific pathology--among them, six lesions with malignant biological behaviour were identified: one microinvasive squamous cell carcinoma and five malignant lymhoproliferative lesions. Usefulness of routine lacrimal sac wall biopsy during surgery for primary acquired lacrimal drainage system obstruction is undoubtful and commensurate with the constant need for better understanding of the pathological processes that involve lacrimal drainage system.