The selective BRAF serine-threonine kinase inhibitor vemurafenib is currently part of the standard treatment arsenal of patients with advanced BRAF-mutated melanomas. The most common adverse effects of vemurafenib are cutaneous events, arthralgia, and fatigue. Neutropenia is observed in fewer than 1% of the patients, and no disseminated intravascular coagulation (DIC), thrombocytopenia, or clotting disorders have been reported in the main clinical trials. 1,2 In this article, we report on a case of vemurafenib-induced DIC in a melanoma patient and combine our findings with information obtained from pharmacovigilance databases. Case Report A 53-year-old man was diagnosed with synchronous metastasized cutaneous melanoma. After excision of the primary tumor, he received dacarbazine, which induced a partial response. Because of rapidly progressive disease 8 months later, he was referred to our hospital. Restaging showed an asymptomatic solitary 9 mm brain metastasis and high hepatic tumor load. The cobas 4800 BRAF V600 Mutation Test (Roche Molecular Diagnostics, Rotkreuz, Switzerland) was positive. Chemistry showed a serum lactate dehydrogenase (LDH) of 3,101 U/L (normal value Ͻ 250 U/L) and a serum S100 calcium binding protein B (S-100B) of 14.65 g/L (normal value Ͻ 0.20 g/L). For additional laboratory studies see Table 1. Vemurafenib 960 mg twice daily orally was started. Six days later, he presented at the emergency room with general malaise, deterioration, and loss of energy due to anemia. Blood tests showed an anemia without evidence of hemolysis, a thrombocytopenia of 37 ϫ 10 3 /L, a prolonged prothrombin time (PT) and activated partial thromboplastin time (aPTT) with decreased fibrinogen and strongly elevated D-dimers (Table 1). Vemurafenib was then interrupted and 6 RBC concentrates were administered over 3 days. All laboratory values normalized spontaneously. His serum LDH and S-100B decreased to 1,154 U/L and 1.74 g/L, respectively, suggesting a massive tumor response. On day 14, vemurafenib was restarted at a 50% dose (480 mg). Approximately 12 hours after taking the first dose of vemurafenib, his platelets dropped from 247 ϫ 10 3 /L to 98 ϫ 10 3 /L, and the PT and aPTT were again prolonged; decreased fibrinogen and elevated D-dimers indicated acute recurrent DIC. Twelve hours later he developed hemiparesis. According to computed tomography imaging, this was caused by bleeding in his known brain metastasis. All medical treatments were stopped, and the patient died within 24 hours.