The diagnosis of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is usually confirmed by genetic testing or skin biopsy. We here report the case of a 69-year-old woman with recurrent transient ischemic attacks (TIAs) and strokes, seizures, and dementia without any mutations in exons 3 and 4 of the Notch3 gene and with a normal skin biopsy, but who showed characteristic CADASIL abnormalities on brain pathological examination. Our findings suggest that negative results in these two tests do not exclude the disease and a leptomeningeal biopsy or a second skin biopsy should be considered in such cases.