The aim of this report was to present a case of interference on prothrombin time (PT) test that directed further laboratory diagnostics and resulted with final detection of monoclonal gammopathy in an 88-year old man. Routine coagulation testing during medical examination at Emergency Department revealed unmeasurable PT (< 7% activity) and activated partial thromboplastin time (aPTT) within reference range. After repeated sampling for coagulation testing, PT was unmeasurable again, as well as fibrinogen level (< 0.8 g/L), thrombin time (TT) was significantly prolonged (107 seconds) and aPTT was within reference range. In both plasma samples refrigerated at 4 ˚C overnight, white gelatinous precipitate was visible between the cell and plasma layers and the presence of monoclonal protein (M-protein) was suggested in our patient. Further laboratory diagnostics revealed total serum proteins at concentration of 123 g/L and the presence of M-protein IgG lambda (λ) at concentration of 47.1 g/L. These results suggested monoclonal gammopathy as an underlying pathophysiological condition in our patient. Activities of coagulation factors II, V, VII and X were within reference ranges or increased. These results and correction of unmeasurable PT result to 67% in mixing test with commercial normal plasma suggest in vitro rather than in vivo interference of M-protein on PT result. In contrast, significantly prolonged TT results in all analysed samples suggest impact of M-protein on this global coagulation test due to possible effect on fibrin polymerization.