Abstract Paraneoplastic coagulopathies are uncommon in patients with lymphoma. We report the first case of an acquired coagulopathy in a patient with isolated primary central nervous system lymphoma (PCNSL) demonstrating large‐cell histology. In our patient, a paraneoplastic factor VII inhibitor significantly delayed a diagnostic lumbar puncture despite fresh frozen plasma and inactivated prothrombin complex concentrate. While her coagulopathy was effectively overcome with recombinant activated factor VIIa and subsequently with lymphoma‐directed therapy, her delayed diagnosis likely contributed to a poor outcome. Our case highlights the importance of rapidly identifying and correcting paraneoplastic coagulopathies when PCNSL is suspected.