A recently described case of putative early tertiary syphilis in a young adult male from 6th century Anglo‐Saxon England exhibits a distinctive endocranial pathology. A case–control study using both clinical and archaeological materials was performed to investigate a possible association of the pathology with syphilis. Scanning electron microscopy and microcomputed tomography were used to image the syphilitic case and normal cranial material.Although the pathology does seem to have an association with syphilis (OR = 13.14), the sample size is small, and the authors caution against overinterpretation of the results. The study confirms observations by other authors suggesting the lesion has some association with a range of pathological conditions. Any association with syphilis seems to be restricted to the early tertiary stages and is possibly absent in the later stages of the disease.The morphological differences present in the samples observed by scanning electron microscopy and microcomputed tomography illustrate the abnormal nature of the vascularity within the syphilitic cranium. The widespread presence of similar lesions within other tubular bones leads the authors to propose hypothesis that unresolved angiogenesis is the underlying mechanism behind the skeletal changes in tertiary syphilis. This angiogenic model accounts for several diverse characteristics in the progression of skeletal disease resulting from infection by spirochetes of the Treponema pallidum family. Copyright © 2012 John Wiley & Sons, Ltd.