Factor V deficiency by acquisition of an inhibitor is a rare pathology whose cause is often idiopathic. The clinical phenotype can range from asymptomatic laboratory abnormalities to life-threatening bleeds. We report a case of acquired factor V deficiency diagnosed in our laboratory, which illustrates the diagnostic procedure and the etiological circumstances. Acquired factor V inhibitors develop in extremely rare cases via the development of alloantibodies or autoantibodies against factor V. Several diseases or conditions are associated with factor V inhibitors. In this observation, the predisposing factor was the autoimmune context; our patient has ulcerative colitis. The biological diagnosis of factor V inhibitors (aFVi) remains a challenge, which every biologist must think about when faced with an isolated FV deficiency not explained by hepatic involvement. It is a rare pathology but its occurrence is worrying for both the biologist and the clinician because of the absence of a validated therapeutic strategy.