Lyme disease is a multisystem tick-borne transmissive disease with heterogeneous manifestations, frequently making the diagnosis difficult in clinical practice. Herein, we report a case of a 43-year-old female patient who presented with generalized lymphadenopathy requiring a further diagnostic evaluation towards lymphoma. The patient also had clinical signs of Sjögren's syndrome. Lymph node excision with subsequent histological and immunohistochemical studies were performed. While light microscopy findings were suspicious for lymphoma, immunohistochemistry results were consistent with cortical and paracortical lymph node hyperplasia with no evidence of lymphoproliferative disorder. Further laboratory testing confirmed the presence of Lyme borreliosis. Effectiveness of the administered antibiotic therapy confirmed Borrelia burgdorferi infection. Interrelationships between Sjögren's syndrome, lymphadenopathy and Lyme disease are discussed.