Monoclonal gammopathy of undetermined significance (MGUS) is considered an asymptomatic precursor of malignant lymphoid disorders. This case series and literature review shows that these monoclonal gammopathies can cause significant morbidity. We describe a patient with angioedema due to acquired C1-esterase inhibitor deficiency, a patient with cryoglobulinemia type II causing skin vasculitis and glomerulonephritis, and a patient with glomerulonephritis and nephrotic syndrome – all caused by a monoclonal gammopathy that can be classified as MGUS. Clinicians should be familiar with these consequences of monoclonal gammopathies. The term MGUS should only be used in patients without organ damage caused by monoclonal gammopathies.