Mikulicz’s disease and Sjögren’s syndrome involve salivary glands. They are characterised by lymphocytic infiltrations in affected exocrine glands leading to their swelling and dysfunction. Although they present similar clinical symptoms, currently they belong to different classifications and require different multidisciplinary treatments. This study presents and compares Sjögren’s syndrome and Mikulicz’s disease and reviews their main clinical, histopathological, and serologic criteria and the methods used in the diagnostic process. The most reliable diagnostic method is histopathologic examination of glandular tissue obtained by either minor or major salivary gland biopsies. Serologic criteria play an additional diagnostic role. The different radiological modalities allow the exclusion of other inflammatory and neoplastic processes that can mimic the initial stages of Mikulicz’s disease and Sjögren’s syndrome.