Bacillus piliformis is a long, rod-shaped bacterium that has never been grown in cell-free medium and whose taxonomic classification is uncertain. B. piliformis is the causative agent of Tyzzer's disease, which is frequently reported in laboratory, wild, and domesticated animals. The spectrum and severity of this disease is wide in animals. Although many infections are rapidly fatal, subclinical infections are also common. To date, there have been no reports of B. piliformis infection in human beings, although elevated antibody levels have been reported in pregnant women. We describe the first case of human B. piliformis infection, in a man with HIV-1 infection and chronic, localized, crested verrucous lesions. The diagnosis was confirmed by ribosomal RNA sequencing. The spectrum of organisms leading to infection and the spectrum of diseases caused by these organisms continue to expand, as new infections are identified and as patients with HIV-1 live longer with more severe immune suppression. The extreme difficulty in culturing B. piliformis and the lack of clinical and histopathologic experience with this organism in human beings mean that B. piliformis is potentially another infectious agent to be considered in human beings. Also, when an infectious organism is a strong clinical consideration, silver stains may be of use when results of routine bacterial staining are negative.