Trichodysplasia spinulosa (TS) is a folliculocentric and clinically papular dermatological disorder occurring in the setting of immunosuppression typically in association with solid organ transplantation or hematolymphoid malignancies. We report the occurrence of TS in a 7-year-old girl with Down syndrome and pre-B-acute lymphoblastic leukemia who was completing chemotherapy at onset. The patient's affected follicles were dilated by an expansion of a dystrophic follicular inner root sheath cell population displaying enlarged trichohyaline cytoplasmic granules and progressing centrally to keratotic and parakeratotic debris, and superficially demonstrating some diminutive hair shaft-like material within the keratotic spicules. Electron microscopic studies of a follicular lesion showed extracellular viral particles suggestive of a polyomavirus within the central follicular keratotic debris. DNA polymerase chain reaction (PCR) and gene sequencing studies, performed on the tissue of the microscopic slide and paraffin block, for the recently identified TS-associated polyomavirus (TSPyV) resulted as positive for TSPyV. PCR for the Merkel cell polyomavirus was negative. To date, this case is unique in representing the first case of TS confirmed by electron microscopy in which a related viral pathogen has been molecularly identified. An additional 19 reported cases classifiable as TS are tabulated and reviewed.