Pathobiologic characteristics of cerebral and cutaneous melanoma may cause an increase in mortality resulting from brain metastases in advanced melanoma patients, in addition to anatomic lesions and biological effects caused by the tumor location. We established intracranial and subcutaneous melanoma models using cultured malignant cells derived from amelanotic melanoma. The median survival times in a mouse model with intracranial tumors was 20 days, but a mouse model with subcutaneous tumors did not show cachexia until they were killed 28 days after inoculation with tumor cells. Histopathological analysis showed that a high karyokinesis phase and nuclear pleomorphism appeared in the intracranial model compared with the subcutaneous tumor model mice. The tumor boron concentration at 2.5 h after boronophenylalanine administration was 15.21±3.88 μg/g in an intracranial melanoma xenograft and 19.85±3.63 μg/g in a subcutaneous melanoma xenograft. Intracranial melanoma showed more malignancy and shorter survival time than did subcutaneous melanoma when the same number of tumor cells were injected, and subcutaneous and intracranial amelanotic malignant melanoma tumors are both fitted for boron neutron capture therapy.