Common variable immunodeficiency (CVID) is the most frequent primary immunodeficiency syndrome in adults with equal sex prevalence. The syndrome typically presents as recurrent infections, with onset in childhood or young adulthood (between 20 and 30 years). CVID patients also have a higher prevalence of autoimmune diseases. A 38-year-old woman presented to the Rheumatology Department with polyarthralgia and fever of 39 degrees C of several months' duration. She had recurrent respiratory and gastrointestinal tract infections and pernicious anemia. Immunological studies showed decreased levels of IgG, IgM, complete IgA deficiency, increased percentage of CD8 lymphocytes, and a reduced CD4:CD8 ratio. HLA-DR typing was performed and we identified HLA-DRB1*01. Adequate intravenous immune globulin substitution as well as antibiotic and anti-inflammatory treatment resulted in the remission of arthritis. Hand radiograms repeated after 12 months showed narrowing of the intra-articular space in the right metacarpophalangeal and radiocarpal joints with multiple bone cysts and erosions. Erosions were found in both humeral heads as well. This prompted the diagnosis of rheumatoid arthritis. Arthritis can be a presenting symptom of primary immunodeficiency in adults, especially when accompanied by recurrent infections or autoimmune diseases. These patients require more advanced diagnostic procedures and therapeutic cooperation of different specialists.