A 46-year-old woman with erythema of the right breast presented to our hospital and was diagnosed with stage IV breast cancer (HER2-positive invasive ductal carcinoma). She received 4 courses of anthracycline-based regimens and 4 courses of trastuzumab + pertuzumab + docetaxel (Tmab + Pmab + DTX). Since she responded well to these therapies, only Tmab + Pmab was continued thereafter. Twenty-three months after starting treatment, she developed a headache. A tumor was identified in the right temporal lobe. Craniotomy was performed for definitive diagnosis. Intraoperative pathological assessment suggested the tumor to be brain metastasis of breast cancer. However, the final pathological diagnosis was diffuse large B-cell lymphoma of central nervous system (DLBCL-CNS) based on re-assessment with immunohistochemical examinations. Therefore, the Tmab + Pmab was discontinued, and 6 courses of high-dose methotrexate therapy were administered. This case highlights the importance of considering rare entities, such as DLBCL, when diagnosing a solitary brain tumor in a patient with a primary cancer, based on imaging and pathological findings.