A case of amelanotic melanoma arising in the upper molar region, which was difficult to diagnose histologically, is reported. The patient was a 79-year-old woman, who complained of a painful swelling in the gingiva of the left upper molar region. Routine histological examination showed that the lesion was composed of diffusely scattered atypical cells with round, spindle-shaped and irregular nuclei and scanty fibrous connective tissue. A fascicular arrangement was often found in the lesion, and no cancer nests were observed. Immunohistochemical study demonstrated positive staining for S-100 protein in both the nuclei and cytoplasm of the tumor cells. Electron microscopic examination revealed that cell organelles were abundant, and an interrupted basal lamina was often found along the cell membrane. The preliminary diagnosis was a non-epithelial malignant tumor. After surgery, histological examination of metastases in lymph nodes from the submandibular region revealed that the tumor cells contained melanin pigment in the cytoplasm, as confirmed by Masson's melanin stain. The final pathological diagnosis was therefore amelanotic melanoma. Immunohistochemical staining for S-100 protein may be useful for differential diagnosis of amelanotic melanoma in conjunction with electron microscopic examination.