Acquired inhibitors of blood coagulation are rare but of clinical importance. Prothrombin is a vitamin K-dependent protein, and acquired antibodies toward prothrombin are often associated with the presence of lupus anticoagulant. We describe a previously healthy 70-year-old man presenting with both hemorrhage and thrombosis as well as a prolonged prothrombin time. At arrival at the hospital, he was diagnosed with deep venous thrombosis, and an enlarged lymph node in the left groin was noted (revealed as follicular lymphoma grade 1 by biopsy). Prothrombin activity and antibody titer were followed for 5 months with 15 sampling time points to monitor the treatment outcome of the patient. Diagnostic work-up identified prothrombin deficiency as cause of bleeding. A nonneutralizing calcium-dependent antiprothrombin antibody was found, suspected to increase the clearance of prothrombin, which has previously only occasionally been reported. Lupus anticoagulant was ruled out and thrombosis was judged to be caused by a combination of malignant disease and stagnant venous flow following enlarged lymph nodes in the groin. This report illustrates how investigation of prolonged global coagulation tests, triggered the diagnosis of a rare but critical condition, immune-mediated prothrombin deficiency. The diagnosis is challenging and involves proper differential diagnosis. image