A 53-year-old man received a diagnosis of stage IV melanoma with metastatic disease to the spine and brain 3 months before presentation. Four weeks following receipt of immunotherapy with ipilimumab and nivolumab, he developed acute abdominal pain in the setting of a rapidly rising lactic acid dehydrogenase levels, prompting hospital admission. Imaging results showed mild disease progression (new ascites and periportal metabolic lymph node). Splenic infarct and portal/splenic vein thrombi were identified as etiologies of his acute pain and were presumed to be secondary to hypercoagulable state of malignancy.