Cryoglobulinemia is a rare illness of cryoglobulin accumulation in the blood which can typically present with arthralgia, purpura, skin ulcers, glomerulonephritis, and peripheral neuropathy. It is classified as mixed cryoglobulinemia when cryoglobulins contain more than one immune component such as IgM rheumatoid factor and polyclonal IgG. Typically, it presents in the setting of clonal hematologic disease, viral infection, or certain connective tissue diseases. Herein, we report the case of a 24-year-old man diagnosed and treated as mixed cryoglobulinemia in the setting of juvenile idiopathic arthritis (JIA). Investigations for viral etiologies, including HBV, HCV, and HIV, and all serologic tests were negative. Additionally serum protein and urine protein electrophoresis did not reveal monoclonal gammopathy; however, testing for plasma cryoglobulins was positive, and qualitative analysis revealed a faint polyclonal pattern. Thus, he was diagnosed with cryoglobulinemia in the setting of JIA, which has not been reported in the literature before. He dramatically improved upon initiation of rituximab and methotrexate.