Seung-Gu Yeo Department of Radiation Oncology, Soonchunhyang University College of Medicine, Soonchunhyang University Hospital, Cheonan, Republic of Korea Abstract: Prophylactic cranial irradiation (PCI) lowers the risk of brain metastasis (BM) and increases survival in small cell lung cancer (SCLC) patients, but it also entails a risk of neurocognitive dysfunction (NCD). One strategy to mitigate this neurotoxicity is hippocampus-avoiding (HA) whole-brain radiation therapy, as the hippocampus is mainly responsible for radiation-related NCD and hippocampal or perihippocampal metastases are rare. A few prospective clinical trials have demonstrated a reduction in NCD following HA whole-brain radiation therapy. The 59-year-old male patient described in this report had limited-stage SCLC and a complete response to thoracic chemoradiotherapy. Seven months after receiving HA-PCI of 25 Gy in 10 fractions using intensity-modulated radiation therapy, a 36 mm solitary metastasis was detected in the right perihippocampal region. The mass was surgically removed but the patient died 2 months later. The development of a solitary HA region metastasis is uncommon, considering that metastasis in this area usually occurs in patients with high numbers of BMs. Our case demonstrates the need for further validation of HA-PCI for SCLC patients in terms of both neurocognitive protection and the absence of compromise in terms of BM prevention. Keywords: hippocampus-sparing, lung cancer, neurotoxicity, cognition, brain metastasis, whole brain radiation therapy